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Volume 110 (1997)
- Issue 6 Pages 303-
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Volume 110, Issue supplement
Displaying 1-38 of 38 articles from this issue
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Yoshimi Okada1997 Volume 110 Issue supplement Pages 1-6
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTransgenic plants are emerging as an important system for the expression of many recombinant proteins, especially those intended for therapeutic purpose. The productin of foreign proteins in plants has several advantages. In terms of required equipment and cost, mass production in plants is far easier to achieve than techniques involving animal cells. Successful production of several proteins in plants, including human serum albumin, haemoglobin, monoclonal antibodies, viral antigens (vaccines), enkephalin, and trichosanthin, has been reported. Particularly, the demonstration that vaccine antigens can be produced in plants in their native, immunogenic forms opens exciting possibilities for the “bio-farming” of vaccines. If the antigens are orally active, food-based “ edible vaccines” could allow econmical production. In this review, I will discuss the progress that has been made by several groups in what is now an expanding area of medicine research that utilizes transgenic plants.View full abstractDownload PDF (5172K) -
Soichi ARAI1997 Volume 110 Issue supplement Pages 7-10
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThis lecture first pinpoints the “tertiary” function of foods which, as opposed to the conventional “primary” and “secondary”functions that are related to nutrition and preference, respectively, is understood to be directly involved in the modulation of our physiological systems such as the immune, endocrine, nervous, circulatory, and digestive systems Insights into this newly defined function are particularly important in that the intake of physiologically functional food factors could be effective in preventing diseases that may be caused by disorders in these systems. Technologically, it has become feasible to design and produce physiologically functional foods (simply, functional foods) that are expected to satisfy in whole or in part our today's demand for disease prevention by eating. Such public expectations are reflected in the activation and development of academic and industrial studies on novel food factors. Meanwhile, a national policy has been established to approve functional foods in terms of “foods for specified health uses”defined by new legislation. Up to now, 78 such items have been approved; the first was a hypoallergenic rice product. Here are highlighted the details of studies on cereal-based functional foods. Other basic and applied studies directed toward the tertiary function of foods, with future perspectives for functional foods, are also discussed.View full abstractDownload PDF (3418K) -
Toshio Shimizu1997 Volume 110 Issue supplement Pages 11-16
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSAs a result of the aging population in Japan, physiologically functional foods, which were first introduced by the project supported by the Ministry of Education of Japan, are expected to play an important role in body defence, prevention and recovery of life-style related diseases. The scientific studies concerning the relationship between food components and health promoted the Ministry of Health and Welfare to establish the system for the food labelling which was used for a “Foods for Specified Health Use” (FOSHU) in 1991. Concerning FOSHU, the terminology, the reguratory provisions, the required criteria for application, the system of approval and the labelling of approval products are summerized in this article. The procedure from application to approval is examplified by Heme-iron beverage for iron deficiency anemia. This product contains heme -iron-enriched amino acid chains which maintain the good absorption of heme-iron from hemoglobin. The health claim approved for this product is “suitable for those who suffer from a mildly anemic condition which may require an iron supplement”View full abstractDownload PDF (4998K) -
Takahisa Tokunaga1997 Volume 110 Issue supplement Pages 17-22
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSSeventy-nine products have been licensed as Foods for Specified Health Use (FOSHU) until 1997 by Ministry of Health and Welfare in Japan. Fifty-two of them are claiming Bifidogenicity and maintaining a good GI condition those which contain indigestible oligosaccharides or Bifidobacterium/Lactobacillus or dietary fiber. New type of FOSHU, concerning suppression of cholesterol absorption, mineral absorption, lowering blood pressure are increased recently.View full abstractDownload PDF (4716K) -
George B. Weiss1997 Volume 110 Issue supplement Pages 23-25
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSCurrent and potential regulations of functional foods (nutraceuticals) will be discussed with emphasis on those features differentiating nutraceuticals from drugs. Current practices in nutraceutical development and limitations on their marketing and acceptance will be summarized. Comparisons between development and marketing strategies used for herbal and plant products and those used for nutraceuticals will be outlined. Finally, conclusions will be derived concerning the status and evolving future prospects for nutraceuticals in the United States.View full abstractDownload PDF (2185K) -
Nobuharu AKATSUKA1997 Volume 110 Issue supplement Pages 26-27
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe Ministry of Health and Welfare, Japan, has recently approved the functional foods for specific health uses. However, most of Japanese clinicians do not know what the “functional foods” are. From the clinical point of view, I will discuss the possible problems with the functional foods and compare their roles with those of foods and drugs.View full abstractDownload PDF (1180K) -
Kunio Torii1997 Volume 110 Issue supplement Pages 28-32
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTaste preferences are altered to reflect physiological needs and to support the recovery from nutritional disorders. The central mechanism both recognition for and adaptation to a deficient essential nutrient, i.e. L-lysine, have been unveiled that the feeding center in the hypothalamus is a primary center nucleus to induce a neuronal plasticity responding to dietary intake of deficient nutrient in the brain and peripherally, such as sense of taste and its concentration change. Changing preferences may act as an alarm, signaling protein malnutrition or metabolic adult disease, such as hypertension for saltiness, diabetes for sweetness, etc. In addition, our consumption of alcohol beverage is still increasing despite of one of candidate to induce the hepatic disorders, because pharmacological function of alcohol in the brain is welcome for people enjoying meal or being relieved from stresses. Preference for both L-alanine and L-glutanine was observed when alcoholic rats fell in the hepatic disorder. Acute alcohol loading induced suppression of motor activity and the hepatic dysfunction, but both amino acids did obviously protect these alcoholic symptoms. People should have to require a little bit more specific L-amino acid physiologically and pharmacologically depending upon different states among aging, lifestyle, metabolic diseases and various stresses.View full abstractDownload PDF (3889K) -
Michio YAMAMURA, Mamoru SUZUKI, Kazuo MATSUMOTO1997 Volume 110 Issue supplement Pages 33-38
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTaltirelin hydrate[1-methyl-(S)-4, 5-dihydroorotyl-L-histidyl-L-prolineamide tetrahydrate] is a new orally active thyrotropin releasing hormone (TRH) peptide analog synthetized from aspartic acid. From preclinical studies with mice and rats, Taltirelin hydrate was found to be highly stable in the blood and brain as compared with TRH. Furthermore, the CNS stimulating actions of Taltirelin hydrate such as antagonistic actions against pentobarbital-induced anesthesia and reserpine induced hypothermia were found to be about 100 times stronger and about 8 times longer-lasting as compared with those of TRH. Meanwhile, the affinity of Taltirelin hydrate for TRH-receptors was about 10 times lower, and the endocrine action was about 5 times less potent than those of TRH. Therefore, high CNS-selectivity and long-lasting action of Taltirelin hydrate would be attributed to its high stability in the body and low affinity for TRH-receptors. Oral administrations of Taltirelin hydrate ameliorated consiousness impairment, memory impairment and motor dysfunction in several models. The clinical studies for patients with spinocerebellar degeneration are in progress.View full abstractDownload PDF (4878K) -
Masami Fukuoka, Tomohiro Ohta, Mamoru Kiyoki1997 Volume 110 Issue supplement Pages 39-43
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe endocrine system to maintain calcium homeostasis involves the active vitamin D, as well as parathyloid hormone (PTH). Based on this ‘classical’ calcium-regulatory function, 1, 25-(OH)2D3 and 1 α OHD3 was developed as the drug for vitamin D resistant rickets, renal dystrophy, and osteoporosis. Psoriasis is a chronic skin disease which is characterized by hyperproliferation and abnormal differentiation of epidermis. As an anti-psoriatic drug, 1, 24R-(OH)2D3 has been on clinical use. The efficacy for psoriasis is explainable by the differentiation-inducing activity of this compound. 1, 25-(OH)2D3 was also reported to suppress proliferation and induce differentiation of tumor cells including breast cancer, colon cancer and so forth, suggesting the possible therapy of malignant tumors. In immune system, active vitamin D3 exerts various effects; 1, 25-(OH)2D3 suppresses proliferation and cytokine production in T cells and antibody production in B cells. Animal models of autoimmune diseases and skin-graft suggest active vitamin D becomes a novel immuno suppressant. Since 1, 25-(OH)2D3 induces the synthesis of nerve growth factor (NGF), it will be a new therapy for the treatment of neuronal degenerative diseases.View full abstractDownload PDF (4329K) -
Akira Orimo, Satoshi Inoue, Osamu Minowa, Kazuhiro Ikeda, Hisahiko Hir ...1997 Volume 110 Issue supplement Pages 44-49
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSEstrogen is involved in the growth and development of female organs such as uterus and mammary gland. On the other hand, from clinical point of view, it is recently suggested that estrogen is effective to protect postmenopausal women from osteoporosis, coronary heart disease and Alzheimer disease. In order to study the molecular mechanism of estrogen action, we have identified an estrogen responsive gene, efp (estrogen-responsive finger protein), which might mediate estrogen action in various target organs at diverse stages and targeted mutagenesis of efp gene could help clarify physiologic actions of estrogen.View full abstractDownload PDF (4862K) -
Kiyoshi MIZUGUCHI, Takashi YANO, Hiroyuki KAWANO, Masato ABEI, Naomi T ...1997 Volume 110 Issue supplement Pages 50-55
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSPolyunsaturated fatty acids (PUFA) regulate various biological functions and are involved in a variety of diseases. Eicosapentaenoic acid (20:5, EPA), one of the ω-3 PUFA, has been reported a number of actions including suppression of platelet aggregability and decrease in serum lipids and is well known to be useful in preventing the atherosclerotic diseases. In this paper, we demonstrated that highly purified ethyl eicosapentaenoate (EPA-E) prevents cholesterol (CH) gallstone formation in hamster model. Repeated administration of EPA-E to animals fed a lithogenic diet for 6 weeks decreased the incidences of both CH crystal and CH gallstone formations in gallbladder bile. Contrary, bezafibrate, one of fibric acid derivative which were reported to increase CH saturation index (CSI) in bile, significantly increased the incidences of CH crystal and gallstone formations. EPA-E did not affect the CSI, but markedly increased biliary phospholipid concentration. In the same model, ethyl palmitate (16:0), ethyl oleate (18:1), ethyl linolate (18:2, ω-6) and ethyl arachidonate (20:4, ω-6) had no effects both on biliary lipids composition and CH gallstone formation. These result suggest the benefit of EPA-E in the prevention of CH gallstone.View full abstractDownload PDF (5123K) -
Yoshihiro Urade1997 Volume 110 Issue supplement Pages 56-58
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSProstaglandin (PG) D2 is a major prostanoid produced in the central nervous system and mast cells, acting as a neuromodulator and an allergic and inflammatory mediator. PGD2 is readily dehydrated to produce PGs of the J series, such as PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12, 14-PGJ2. We identified two distinct types of PGD synthase: one is glutathione independent, the lipocalin-type enzyme; and the other is glutathione-dependent, the hematopoietic enzyme. Lipocalin-type PGD synthase is localized in the central nervous sytem and genital organs, dominantly produced in the leptomeninges of the brain and pigmented epithelium of the retina, and is actively secreted as β-trace into the cerebrospinal fluid and interphotoreceptor matrix, respectively. Since the enzyme binds all-trans or 9-cis-retinoic acid with Kd of about 100 nM, it is considered to be a bifuncxional protein acting as a PGD2-producing enzyme and an extracellular retinoid-transporter. Alternatively, we recently cloned the cDNA for hematopoietic PGD synthase, crystallized the recombinant enzyme, and determined the three-dimensional structure. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family.View full abstractDownload PDF (2561K) -
Kunio Shiota, Kwan-Sik Min, Tomoya Ogawa1997 Volume 110 Issue supplement Pages 59-62
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSEquine chorionic gonadotropin (eCG) and luteinizing hormone (eLH) are encoded by a single gene and have identical peptide portions. They, however, differ in the structures of their attached oligosaccharides, which depend on the sites of their production. Recombinant eCG/LH (rec-eCG/LH) possesses dual LH and FSH activities. Mutant eCG/LH in which Asn 56 of the α-subunit was changed to Gln to remove the N-linked oligosaccharide showed complete loss of LH activity, whereas in contrast its FSH activity was more potent than that of the wild-type. Another mutant, which lacked the carboxyterminal portion of the β-subunit to which O-linked oligosaccharides are attached, showed LH activity similar to that of the wild-type, whereas it had the most potent FSH activity. Thus, the oligosaccharides attached to eCG/LH play differential roles in the expression of biological activity.View full abstractDownload PDF (2927K) -
Takenori Natori, Kohzi Akimoto, Kazuhiro Motoki, Yasuhiko Koezuka, Tat ...1997 Volume 110 Issue supplement Pages 63-68
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSNew glycosphingolipids, named agelasphins, have been isolated as antitumoral compounds from an extract of a marine sponge, Agelas mauritianus. The absolute configurations of agelasphins were elucidated by the total synthesis. Various analogues of agelasphins were also synthesized and the relationship between their structures and biological activities was examined using an MLR assay. From the results, KRN7000, (2S, 3S, 4R)-1-O(α-D-galactopyranosyl)-2-(N-hexacosanoylamino)-1, 3, 4-octadecanetriol, was selected as a candidate for clinical application. KRN7000 markedly stimulated lymphocytic proliferation in allogeneic MLR, and showed potent tumor growth inhibitory activities in B16-bearing mice and strongly inhibited tumor metastasis, suggesting that KRN7000 is a potent biological response modifier. These biological effects were exerted by the activation of dendritic cells by KRN7000.View full abstractDownload PDF (4878K) -
Hiroshi Hatanaka, Kyoichi Shimomura1997 Volume 110 Issue supplement Pages 69-74
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSMicrobial products have amazing diversity and complexity in their chemical structures as well as in their biological activities. The successful discovery and development of FK506 (Tacrolimus) adds a new example showing that microbial products are agents with potential therapeutic benefits.
In 1984, we found a novel immunosuppressant FK506 during the course of our research program for discovery of specific inhibitors on IL-2 production in the microbial products. FK506, a new class of 23-membered macrolide lactone, was isolated the fermentation broth of Stmptomyces tsukubaensis No.9993. This agent strongly inhibited the proliferative response of lymphocytes to alloantigen stimulation, and a variety of T cell associated immune reaction. FK506 also suppressed immune responses in vivo as well as in vitro and this immunosuppressive effect was more highly potent than cyclosporin, a well-known fungal metabolite. The profound immunosuppressive properties of FK506 were subsequently explored in organ transplantation in animal models. Clinical trials of FK506 were begun in 1989 by Professor Stazl and his colleagues at the University of Pittsburgh. Since then wider evaluation of FK506 in a variety of transplantation fields has been performed globally; in North America, Europe and Japan. In 1993, FK506 was commercialized in Japan for prevention of liver transplant rejection. FK506 is also undergoing extensive evaluation as an agent for the treatment of various autoimmune diseases.View full abstractDownload PDF (4254K) -
Tomoyuki Fujioka1997 Volume 110 Issue supplement Pages 75-80
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESS1)Repeated administration of pravastatin significantly increased serum and liver cholesterol in rats. Hepatic LDL receptor activity was not changed and VLDL cholesterol secretion from the liver was increased. Net cholesterol synthesis in rat liver was increased after 7 days of repeated pravastatin administration. These results suggest that for rats, unlike other animals for which serum cholesterol is decreased, induced HMG-CoA reductase activity due to pravastatin treatment might overcome the inhibitory capability of pravastatin. 2) In the course of screening for squalene synthase inhibitors, novel zaragozic acids -F10863A, B, C and D-containing zaragozic acid D3 were isolated. F10863A was most potent and selectively inhibited cholesterol synthesis in freshly isolated rat hepatocytes among several cultured and isolated cells. It also showed in vivo serum cholestrerol-lowering effects in hamsters and marmosets. However, the inhibition for squalene synthase proved to cause acidosis due to the accumulation of farnesol-derived dicarboxylic acids in urines. 3) A novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A, a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent, was isolated from the fermentation broth of Stachybotrys bisbyi. It inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.View full abstractDownload PDF (3927K) -
Satoshi NAKANISHI, Yuzuru MATSUDA1997 Volume 110 Issue supplement Pages 81-86
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSMicroorganisms are beneficial as a source of natural products in the following sense, diversity of species, versatility and variety of substrates, and unique productivity. On top of them, advantage for industrial utilization of microorganisms is that mass production is feasible by culturing them in a fermentation tank. We have been looking for new substances which interact with a molecule involved in biological responses in animal cells. Among them, we summarize our kinase inhibitors isolated from microbial culture in this paper.View full abstractDownload PDF (5238K) -
Jong-Chl CYONG1997 Volume 110 Issue supplement Pages 87-92
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe action mechanisms of Toki-shakuyakusan(TSS), one of Kampo -herbal medicine, on the clearance of immune complexes and macrophage function were investigated.
In the in vivo study, oral administration of TSS enhanced the immune complexes clearance from the circulation in MRL Mp-lpr/lpr mice and C3H/He mice, but no effect was observed in the carbon clearance assay. In the in vitro study, TSS increased the binding of immune complexes to macrophages or Kupffer cells, and the digestion of immune complexes by Kupffer cells. By flow cytometric analysis, the expressions of Fcγ ll/lll receptors and complement recepter 3 (CR3) on macrophages were increased by the treatment with TSS.
Besides, it was also reported that the appearance of the activity was owe to the combination of Angelicae Radix and Atractylodis Lanceae Rhizoma, two of six ingredients of 'MS. Both outer and inner dialysate of the extract of Angelicae Radix and Atractylodis Lanceae Rhizoma potentiated the binding of immune complexes to macrophages. Low molecular fraction was further fractionated by using colomn chromatography, and the active components were concentrated in fraction 5-C (named LMW5-C).
In conclusion, one of the mechanisme of enhancement of immune complexes clearance was thought to due to increase the immune complexes binding to macrophage though augment of FcTγ ll/lll receptors and CR3 expression. And it was revealed that the active components were not only high moleculer substances but low molecular ones.View full abstractDownload PDF (4543K) -
Hiromichi SUMIYOSHI1997 Volume 110 Issue supplement Pages 93-97
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSAccording to the recent pharmacological findings, garlic is a preventive rather than therapeutic. Epidemiological studies in China, Italy and USA showed the inverse relationship between stomach and colon cancer incidences and dietary garlic intake. Anti-carcinogenic activities of garlic and its constituents including sulfides and S-allyl cysteine, have been demonstrated using several animal models. Garlic preparations has been also shown to lower serum cholesterol and triglyceride levels, which are major risk factors of cardiovascular diseases, through inhibition of their bio-synthesis in the liver, and to inhibit oxidation of low density lipoprotein. Furthermore, in vitro and in vivo studies have revealed that aged garlic extract stimulated immune functions, such as proliferation of lymphocyte, cytokine release, NK activity and phagocytosis. More recently, aged garlic extract has been demonstrated to prolong life span of senescence accelerated mice and prevent brain atrophy.
Manufacturing processes significantly affect chemical constituents in garlic preparations. Different forms contain different phytochemicals and may have different effects and toxicities. For example, aged garlic extract inhibited t-BuOOH-induced oxidation, whereas raw garlic stimulated the oxidation. Although garlic has been used as a condiment and folklore for a long time, it has been noted to cause adverse reactions, such as stomach ulcer and anemia. Among the garlic preparations, only aged garlic extract has been proven to be safe through toxicological studies Thus, aged garlic extract could be the most promising garlic preparation for disease prevention.View full abstractDownload PDF (4184K) -
Miyato Higaki, Fumio Eguchi, Yasuo Watanabe1997 Volume 110 Issue supplement Pages 98-103
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThere have been some reports suggesting the effectiveness of medicinal mushrooms in not only keeping health but also preventing and curing diseases as well as recovering from illnesses. However, no uniformity has been observed with its medicinal effect and thus there are some problems in these materials from clinical aspects. Ununiformity of constituents which has resulted from the lack of established optimum culturing methods and inadequacy of experimental approaches are given as the causes of the problems. In the present study, the authors established a culturing method for harvesting fruit bodies with stable constituents by the use of the best cytogenetical technique for Agaricus blazei(CJ-01)which has attracted special interest recently among medicinal mushrooms. Fundamental medical scientific researches have been conducted with the medicinal effect of Agaricus blazei(CJ-01)obtained by the new culturing method by the widely use of immunological and pharmacological approaches. Based on the results of these studies, the author demonstrated the effect scientifically on the cases where the effect had already been observed clinically (hypertension, atopic dermatitis and diabetes).View full abstractDownload PDF (5207K) -
Akinori UENO, Sachiko OH-ISHI1997 Volume 110 Issue supplement Pages 104-107
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSWe found the time-dependent induction of the systemic hypotensive response to des-Arg9bradykinin and the contractile response of ileum of rats to des-Arg9-bradykinin. Both induced responses to des-Arg9-bradykinin were inhibited by treatment with a Bl receptor competitive antagonist, while the responses to bradykinin was constant throughout the experiment and was not influenced by the B1 antagonist, suggesting that these responses occur via a B1 receptor. The potencies of des-Arg9-bradykinin in these responses were comparable to those of bradykinin at a molar base. The other characteriscs of this phenomenon is that several hours were required to the induction of these responses. In a case of hypotensive response, intravenous LPS pretreatment was necessary, but not for the induction of contraction in ileum preparation. Treatment with actinomycin D or cycloheximide throughout the experiment supressed the induction of the contractile response to des-Arg9-bradykinin. The expression of B1 receptor gene was also confirmed by a RT-PCR method. Therefore, we concluded that these responses to des-Arg9-bradykinin occurred via a B1 receptor, which could be newly generated time dependently.View full abstractDownload PDF (4013K) -
Hiroaki SHIRAHASE, Mamoru KANDA, Katsuyuki MURASE, Shohei NAKAMURA, Hi ...1997 Volume 110 Issue supplement Pages 108-113
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSIn the present study, it was demonstarated that SP, neurokinin A (NKA), neurokinin B (NKB), SP methyl ester (SPME), [Ala5, β -Ala8]- α -neurokinin fragment 4-10 (AANF) at 10-8 M all caused contraction in non-contracted endothelium-intact arteries. SP- and SPME-induced contraction were reduced by removal of endothelium. All the peptides with the exception of AANF induced transient relaxation in the precontracted arteries. The relaxation were attenuated by removal of endothelium. The potency orders for endothelium-dependent contraction (EDC), -dependent relaxation (EDR) and -independent contraction (EIC) were SP>SPME>>NKA≈NKB≈AANF, SP>SPME>NKA>NKB>>AANF and NKA>AANF>NKB>>SP≈SPME, respectively. SP-induced EDC and EDR were attenuated by an NK1 antagonist but not by an NK2 antagonist. The SP-induced EIC was reduced by an NK2 antagonist. SP-induced EDC was attenuated by aspirin, OKY-046, and S-1452. The EDR way attenuated by L-NAME and methylene blue. The EDC induced by SPME was non-competitively attenuated by CP-99994, an NK1 antagonist. EDR was competitively inhibited by CP-99994. In conclusion, SP and related peptides caused EDC via NK1 receptors and TXA2 production, EDR via NK1, receptors and NO release and EIC via NK2 receptors in rabbit intrapulmomary arteries.View full abstractDownload PDF (4932K) -
Katsuya DEZAKI, Hiroshi TSUNEKI, Ikuko KIMURA1997 Volume 110 Issue supplement Pages 114-119
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSWe have found that non-contractile slow Ca2+ mobilization (RAMIC; Receptor-Activity Modulating Intracellular Ca2+) is generated by motor nerve stimulation with anti-cholinesterase at the skeletal muscle, and desensitizes muscle nicotinic receptor (nAChR). To confirm this Ca2+ mobilization without anti-cholinesterase, acetylcholine (ACh) was locally applied by N2 gas pressure onto endplate region at the mouse phrenic nerve-diaphragm muscle preparation. ACh (0.1-3 mM, 20 μl) elicited bi-phasic elevation of [Ca2+]i (fast and slow Ca2+ mobilization measured as Ca2+ -aequorin luminescence) in muscle cells. The peak amplitude of slow Ca2+ mobilization (not accompanied by contraction) was increased by ACh concentration-dependently, whereas that of fast component (accompanied by contraction) reached a maximum response at a lower concentration of ACh. The slow Ca2+ mobilization was blocked by lower concentrations of competitive nAChR antagonists which did not affect the fast Ca2+ transients. Moreover, the slow Ca2+ signal was selectively depressed by a neuronal nAChR antagonist methyllycaconitine. Neither Ca2+ channel blockers nor a Na+ channel blocker tetrodotoxin prevented the generation of the slow Ca2+ mobilization. These results suggest that RAMIC is mobilized through postsynaptic neuronal nAChR subtype to desensitize muscle nAChR at the neuromuscular junction.View full abstractDownload PDF (4733K) -
Yoichiro ISOHAMA, Hirofumi KAI, Takeshi MIYATA1997 Volume 110 Issue supplement Pages 120-125
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTraditional herbal medicines, Kampo medicines in Japan, are composed of various herbs with ubiquitous pharmacological activities. We previously found that Bakumondo-to stimulates phosphatidylcholine (PC) secretion from alveolar type II cells. To define the regulatory mechanisms involving in the Bakumondo-to-induced PC secretion, we investigated the effect of Bakumondo-to on signal transduction systems in alveolar type II cells, Bakumondo-to-induced PC secretion was completely inhibited by each of H-89, H-7 or BAPTA-AM, protein kinase A (PKA), protein kinase C (PKC) or intracellular Ca2+ inhibitor. In addition, Bakumondo-to increased cellular cyclic AMP content and Ca2+ content, too. These results suggested that the secretagogue effect of Bakumondo-to may be coupled to the synergistic cross-talk between cyclic AMP- and Ca2+ -dependent system. To investigate if there is cross-talk between different signaling systems in type II cells, we examined the combined effects of various secretagogues on PC secretion. The combination of terbutaline and PMA potentiated stimulation of secretion, although the effects of terbutaline with A23187, or PMA with A23187 were additive. This synergism seemed to be mediated by Ca2+ influx, because this combination significantly increased cellular Ca2+ content.
These findings suggested that there is synergistic cross-talk between PKA- and PKC dependent signaling system in alveolar type II cells, and that Bakumondo-to may stimulate PC secretion through this cross-talk.View full abstractDownload PDF (4276K) -
Eiichi TACHIKAWA, Kenzo KUDO, Takeshi KASHIMOTO, Eiji TAKAHASHI1997 Volume 110 Issue supplement Pages 126-131
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSWe investigated the effects of root of Panax ginseng C. A. Meyer on the secretion of catecholaniines (CAs) from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh). In two major parts, nonsaponin and crude saponin fractions from the root, the crude saponin but not the non-saponin greatly reduced the ACh-evoked secretion. Furthermore, various purified ginseng saponins (ginsenosides) had a tendency to reduce the secretion. Most effective saponin was ginsenoside (G) RG2. GRg2 also inhibited the ACh-evoked Na+ and Ca2+ influxes into the cells. The GRg2 inhibition of the secretion was overcome by increasing the external Na+ but not Ca2+ concentrations. However, GRg2 did not affect the secretion from the cells induced by high K+, which is regarded as directly depolarizing the cell membranes and causing Ca2+ influx through voltage-sensitive Ca2+ channels. Therefore, the root of Panax ginseng contains ingredients, that is saponins, which inhibit the secretion of catecholanines from the cells stimulated by ACh. The inhinition is probably due to the antagonism of nicotinic acetylcholine receptor-operated cation channels. GRg2 had no effects on other receptor stimulation-responses but GRg3 inhibited them. These may be why the root of Panax gingseng has a variety of pharmacological effects.View full abstractDownload PDF (4498K) -
Yuta KOBAYASHI, Jia SHEN, Song-Hua LI, Eiichi KAKIZOE, Hideki OKUNISHI ...1997 Volume 110 Issue supplement Pages 132-137
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSDulcitol was isolated chemically from Celastrus obiculatus Thumb and determined by HPLC. Effects of dulcitol were examined on collagen-induced arthritis (CIA) in DBA/1J mice. From 6 weeks after the first immunization with bovine type II collagen, dulcitol (100mg/kg body weight/day) was administered orally to immunized mice for 9 weeks. Clinical score of CIA was improved significantly by dulcitol intervention compared with the non-treated CIA mice. Radiographic score of phalangeal destruction was also improved by dulcitol treatment. These findings suggest that dulcitol may play a role in regulation of some inflammatory responses in the present arthritis model. Significant reduction of percentage of CD4+ and CD8+ T cell subsets in the spleen leucocytes of CIA mice was observed by flowcytometry. Almost normal level of CD4+ and CD8+ T cells was observed in dulcitol-treated groups, suggesting T cell-modifying effect of dulcitol in CIA. Weight of spleen was larger in CIA mice and it was not affected by dulcitol. Anti-collagen antibody titer was increased in CIA mice, and it was not affected by dulcitol, either. Improvement of the changes of CD4+ and CD8+ Tcells in the spleen by dulcitol may suggest its modulatory effect on cellular immunity.View full abstractDownload PDF (5500K) -
T. Yamasaki, Benjamin H. S. Lau1997 Volume 110 Issue supplement Pages 138-141
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSOxygen radical injury and lipid peroxidation have been suggested as major causes of cancer, atherosclerosis and the aging process. We examined in vitro the effect of garlic on H2O2-induced oxidant injury in bovine pulmonary artery endothelial cells (PAEC). After overnight preincubation with Aged Garlic Extract (AGE, from Wakunaga Pharmaceutical Co., Ltd., Japan) or S-allyl cysteine (SAC), PAEC monolayers were exposed to H2O2 for 3 h. Cell viability (MTT assay), lactate dehydrogenase (LDH) release, and lipid peroxidation (TBA-RS) were measured to assess oxidant injury. AGE (1-4 mg/ml) pretreatment significantly reduced the loss of cell viability induced by 50-100 μM of H2O2. AGE and SAC exhibited dose dependent inhibition of both LDH release and TBA-RS production induced by 50 μM of H2O2. The results show that AGE and SAC can protect vascular endothelial cells from oxidant injury. Numerous garlic compounds could be involved in the antioxidant properties of garlic, while there could be some prooxidant compounds derived from garlic. It is important to keep an array of antioxidant compounds to develop good herbal preparation, like AGE.View full abstractDownload PDF (3210K) -
Yasuyuki NOMURA, Takashi ARIMA, Tsuneo NAMBA, Masao HATTORI, Shigetosh ...1997 Volume 110 Issue supplement Pages 142-147
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSEffect of the long-term treatment with a Dan-Shen (Salviae miltiorrhizae radix) methanol extract (DME) or its major ingredient lithospermate B (LSB) on memory and learning in scenescence-accelerated mouse (SAM) was investigated by means of Morris's water maze task. DME or LSB treatment significantly decreased the escape latency in the P8 strain of SAM (SAMP8), which strain spontaneously develops learning deficits. These results suggest that DME and LSB treatment improved spacial learning. Neurochemical investigations indicated that both drugs did not affect the cholinergic system, but enhanced functions of the glutamate-PKC system in hippocampus, since the increases in [3H]MK-801 ((+)-5-methyl-10, 11-dihydro-5H-dibenzo[a, b]-cyclohepten-5, 10-imine maleate) binding in cortex and [3H]PDBu (phorbol 12, 13-dibutyrate) binding in hippocampus were observed in DME and LSB treatments. Our previous studies indicate the decrease in PDBu binding and NMDA receptor-mediated functions in SAMP8 brain. Thus, it is suggested that 1) Methanol extract of Dan-Shen is effective for prevention of spacial learning deficit caused with aging, 2) lithospermate B is one of the active ingredients, 3) SAMP8 is useful model animal to investigate drugs for anti-aging or anti-dementia.View full abstractDownload PDF (5357K) -
Kiyoshi MURATA, Kazuhiko SEYA, Izumi MIKI, Hisae JUNKE, Shigeru MOTOMU ...1997 Volume 110 Issue supplement Pages 148-152
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSWe investigated the pharmacological properties of pteleprenine, a quinoline alkaloid contained in the Rutaceous plant, Orixa japonica, on the contractile responses of the guinea pig ileum and on the inotropic responses of the canine left atrium. Contractile responses of the ileum to acetylcholine and histamine were not inhibited by less than 10-6 M of pteleprenine. Meanwhile, the nicotine induced-contraction of the ileum was dose-dependently diminished by pteleprenine, but the contractile response to nicotine did not reach the maximum value in the presence of 10-5 M of pteleprenine. The pA2 value of pteleprenine was 6.6 as determined from the Schild plot, which slope was nearly unity. Furthermore, the contraction of the ileum by 10-5 M of 1, 1-dimethyl-4-phenylpiperazinium (DMPP), a specific agonist of nicotinic acetylcholine receptors, was also dose-dependently suppressed by pteleprenine. On the other hand, 10-5 M of pteleprenine did not have considerable inhibitory effects on acetylcholine- and nicotine-induced negative inotropic effects in the canine left atrium. From these results, it is suggested that pteleprenine has a specific inhibitory effect on nicotinic acetylcholine receptors in the guinea pig ileum.View full abstractDownload PDF (3334K) -
Ken-Ichi FURUKAWA, Nattaya CHAIRUNGSRILERD, Tomihisa OHTA, Shigeo NOZO ...1997 Volume 110 Issue supplement Pages 153-158
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSA crude methanolic extract of the fruit hull of Garcinia mangostana L. inhibited the contraction of the isolated rabbit aorta induced by histamine and serotonin. The extract has been fractionated by silica gel chromatography, monitoring the pharmacological activity to give active compounds. On the basis of physicochemical data, the active substances were identified as amangostin and γ-mangostin. To define the pharmacological properties of α-mangostin, the effect of α-mangostin on both histamine H1 and H2 receptors were examined by monitoring the mechanical responses of smooth muscles and measuring the radioligand binding to cultured vascular smooth muscle cells. The results suggest that α-mangostin acts as a selective and competitive histamine H1 receptor antagonist. The pharmacological actions of γ-mangostin on 5-HT receptors were also investigated by using contractile response of vascular smooth muscle, platelet aggregation and radioligand binding studies. The results provide the evidence that γ-mangostin is a selective and competitive 5-HT2A receptor antagonist. It is of great interest that the structures of α-mangostin and γ-mangostin free from nitrogen atom are not resemble to the common structures of histamine and serotonin receptor antagonists. α-Mangostin and γ-mangostin may become novel types of lead compounds for histamine and serotonin receptor antagonists.View full abstractDownload PDF (4386K) -
Yoshimi Misu, Yoshio Goshima, Takeaki Miyamae, Nobuya Furukawa, Yoko O ...1997 Volume 110 Issue supplement Pages 159-164
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSDOPA has been proposed to be a neurotransmitter of the primary baroreceptor afferents terminating in the NTS and a neuromodulator in striata of rats. Pre- and post-synaptic recognition sites for DOPA itself may exist. DOPA methyl ester (DOPA ester), a potent competitive antagonist for DOPA in continuously superfused slices or within a several min when microinjected in the NIS has some limitation in in vivo use because of its unstableness as a prodrug for DOPA. We have explored to find stable and potent antagonists for DOPA. At first, we tried to clarify whether or not newly synthesized DOPA esters with bulky structure such as DOPA cyclohexyl ester (CHE), DOPA cyclopentyl ester (CPE) and DOPA cyclopentyldimethyl ester (CPDME) antagonize depressor responses to DOPA microinjected into the NTS, and to what degree these analogues 1 μM perfused via probes are converted to DOPA during striatal microdialysis in urethane-anesthetized rats. Then, we analyzed mode of antagonism of some candidate in the NTS system. During striatal microdialysis, DOPA ester 1 μM increased extracellular levels of DOPA to an 100 fold higher level at a peak of the 1st 20 min sample after the perfusion. Conversion ratio of CHE, CPE and CPDME, compared to DOPA ester, was less than 1/5 at the peak of the 3rd sample, 1/3.3 at the peak of the 2nd, and 1/2.7 at the peak of the 3rd, respectively. In the NTS, all analogues 1 μg microinjected abolished depressor responses to DOPA 60 ng. Time required to recover abase was 20 min for CHE and 10 min for DOPA ester, CPE and CPDME. At 100 ng, CHE inhibited peak depressor responses to DOPA 60 ng by 53%, CPE by 40%, and CPDME by 24%, compared to DOPA ester by 22%. Then, DOPA 10-300 ng microinjected produced dose-dependent hypotension. DOPA ester 300 ng, microinjected 1 min previously, shifted a dose-response curve for DOPA 30-300 ng to the right without reduction of the maximum response, showing a competitive mode of antagonism. CHE 30 ng competitively antagonized depressor responses to DOPA 18-300 ng without reduction of the maximum response. CHE 100 ng further shifted the dose-response curve for DOPA 18-100 ng to the right with 25% reduction of the maximum response. Antagonistic activity of CHE 100 ng was equipotent with DOPA ester 300 ng. CHE is a competitive antagonist including partially some noncompetitive components. A possible component might be related to NMDA receptors, since high concentrations of CHE displaced selective binding of [3H]-MK-801, an antagonist. In conclusion, CHE is suitable for the purpose.View full abstractDownload PDF (5269K) -
Yixue XUE, Nu Nu Aye, Keitaro HASHIMOTO1997 Volume 110 Issue supplement Pages 165-170
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSDHA-Ascorbic acid (DHA-As), a new derivative of docosahexaenoic acid (DHA) was tested for its possible antiarrhythmic effects on coronary artery ligation/reperfusion arrhythmias in rat hearts, and adrenaline-induced arrhythmias in canine hearts. DHA-As (3 mg/kg i.v.) did not change the total duration of VT, and tended to suppress the incidence of VT, VF and mortality of reperfusion in rat hearts. The heart rate, QT90 and systolic blood pressure did not change, and the diastolic blood pressure was decreased by DHA-As in the rat hearts. DHA-As significantly decreased the arrhythmic ratio only at two time points (14 and 15 min after injection), and also decreased the heart rate and mean blood pressure in canine hearts. In conclusion, DHA-As tended to suppress the reperfusion-induced arrhythmias in rat hearts. However, the change was not statistically significant. In addition, DHA-As has a weak suppressing effect on adrenaline-induced arrhythmia.View full abstractDownload PDF (4130K) -
Masahiko HIRAFUJI, Takashi EBIHARA, Fumito KAWAHARA, Marito TSUNODA, N ...1997 Volume 110 Issue supplement Pages 171-176
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThere are increasing evidences that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders including hypertension. Docosahexaenoic acid (DHA) may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study was to clarify the in vitro effect of DHA on vascular smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca+2 dynamics which involves in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on the cell growth, and cell hypertrophy induced by angiotensin II as measured by flow cytometer. DHA did not have a significant effect on interleukin-1 β (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP. However, the treatment of smooth muscle cells with DHA (30 μM) for 2 days significantly suppressed the increase in the intracellular Ca2+ concentration induced by 5-hydroxytryptamine, angiotensin II, depolarizing concentration of KCl, but not by thapsigargin. This suppression seems to be due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results suggest that DHA specifically suppresses receptor-mediated Ca2+ influx in smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.View full abstractDownload PDF (4765K) -
Tomotaka Nakamura, Masao Moriya, Naoko Murakoshi, Yoshio Shimizu, Masa ...1997 Volume 110 Issue supplement Pages 177-182
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe effects of phenylalanine (PHE) and tyrosine (TYR) on cold acclimation were studied in mice of the ddY strain. At 5 weeks of age, mice were maintained at 4°C for 4 weeks. Test groups of mice were supplied with a 0.05% (w/v) solution of PHE or TYR as drinking water in addition to water. We measured changes in body weight, intake of water and food, rectal temperature upon acute exposure to -20°C, weight of interscapular brown adipose tissue (BAT) and the levels of glucose, nonesterified fatty acids (NEFA) and 3H-butyrate in the blood prior to and after exposure to the lower temperature of -20°C. Chronic exposure to cold (4°C) reduced body-weight gain for the first two weeks but weight gain recovered within the next two weeks. PHE and TYR partially inhibited the gain in body weight under exposing to cold TYR reduced the gain of body weight under room temperature. Exposure to cold stimulated the daily consumption of food Both PHE and TYR somewhat enhanced the food intake when exposed to cold. Exposure to cold rendered mice resistant to severe cold (-20°C). Both PHE and TYR did not reduce this resistance except in the early state in the case of TYR. Exposure to cold increased the weight of BAT but both PHE and TYR prevented this increase. The effect of TYR was determined in the case fed under room temperature. Cold exposure changed the utilization of glucose, NEFA and 3H-butyrate in the blood when exposed to severe cold (-20°C). Both PHE and TYR prevented the change in NEFA. It remains to be confirmed whether the growth of brown adipocyles is always necessary when mice acclimate to cold.View full abstractDownload PDF (5471K) -
Masaji Saitoh, Masao Moriya, [in Japanese], Naoko Murakoshi, Yoshio Sh ...1997 Volume 110 Issue supplement Pages 183-188
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe effects of adenosine (ADO) and adenine (ADE) on cold acclimation were studied in mice of the ddY strain. At 5 weeks of age, mice were maintained at 4°C for 4 weeks. Test groups of mice were supplied with a 0.05% (w/v) solution of ADO or ADE as drinking water in addition to water. We measured changes in body weight, intake of water and food, rectal temperature upon acute exposure to -20°C, weight of interscapular brown adipose tissue (BAT) and the levels of glucose, nonesterified fatty acids (NEFA) and 3H-butyrate in the blood prior to and after exposure to the lower temperature of -20°C. Chronic exposure to cold (4°C) reduced body-weight gain for the first two weeks but weight gain recovered within the next two weeks. ADO partially but selectively inhibited the gain in body weight. This effect was marked in mice maintained at room temperature. Such an inhibiyory effect was the case of ADE in the room temperature. Exposure to cold stimulated the daily consumption of food ADO further and selectively enhanced food intake, but ADE enhanced that in room temperature. Cold increased in daily intake of water. Both ADO and ADE accelerated the intake of water. This effect was marked in mice maintained at 4°C and the effect of ADE was considerable. Mice chose to drink the water that contained ADO, while the choice of water that contained ADE was apparent only during exposure to cold Exposure to cold rendered mice resistant to severe cold (-20°C). ADO and ADE partially reduced this resistance. Exposure to cold increased the weight of BAT but ADO selectively prevented this increase. Cold did not change the levels of the various compounds measured in the blood. In mice exposed to 4°C for 4 weeks, acute exposure to severe cold decreased the glucose level and increased the levels of NEFA and 3H-butyrate. ADO selectively prevented the changes in the levels of NEFA and 3H-butyrate. It remains to be confirmed whether the growth of brown adipocytes is always necessary when mice acclimate to cold.View full abstractDownload PDF (5119K) -
Norimichi NAKAHATA, Mun-Chual RHO, Yasushi OHIZUMI1997 Volume 110 Issue supplement Pages 189-194
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSZooxanthellatoxin-A (ZT-A), a bloactive substance isolated from a symbiotic marine alga Symblodlnlum sp., caused rabbit platelet aggregation. ZT-A-induced aggregation was dependent on the presence of external Ca2+, and was inhibited by several Ca2+ channel antagonists except Ltype one. Furthermore, ZT-A-Induced aggregation was attenuated by genistein, indomethacin and SQ29548, indicating that tyrosine phosphorylation and thromboxane A2 (TXA2) are involved in the aggregation. In fact, ZT-A released arachidonic acid and accumulated TXB2, a stable metabolite of TXA2, which was inhibited by genistein. ZT-A caused phosphorylation and activation of mitogenactivated protein kinase (MAPK), which was known to activate cytosolic phospholipase A2 (cPLA2). ZT-A caused the activation of phospholipase C (PLC) -γ2, resulting in an accumulation of diacylglycerol that activates protein kinase C (PKC). The MAPK activation was inhibited by genistein and staurousporine. ZT-A is not a Ca2+-ionophore, since its different responsibility from ionomycin to external Ca2+, indomethacin and 12-HETE, a platelet lipoxygenase product. These results suggest that ZT-A stimulates a tyrosine kinase with influxed Ca2+, resulting in the activation PLC-γ2 that stimulates PKC via diacylglycerol. Then, MAPK is activated by a PKC pathway, then cPLA2 is activated by MAPK. The released arachidonic acid is rapidly converted to TXA2 which causes platelet aggregation.View full abstractDownload PDF (5129K) -
Shigetoshi OIKI, Ikunobu MURAMATSU, Shigeki MATSUNAGA, Nobuhiro FUSETA ...1997 Volume 110 Issue supplement Pages 195-198
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSA highly cytotoxic extract from marine sponge, polytheonamide B, is a linear 48-residue peptide. Alternative D-and L-forms of unusual amino acids suggest formation of β-helix that is stable in membrane and serves for ion conducting pore. The NMR study indicated that polytheonamide B forms β-helix in methanol/chloroform solution. Channel activity of polytheonamide B was examined using planar lipid bilayers. Ionic current appeared from pM concentration. Measurements of the reversal potentials revealed that the channel showed cation selectivity. Single channel current was recorded in symmetrical 1 M solutions. The selectivity sequence was: H+>Cs+>Rb+>K+>Na+. Single-channel I-V curve exhibited slight inward rectification. Voltage-dependent transitions between brief openings and long closures were observed. Orientation of the peptide in the membrane was fixed when the peptide was added to one side of the chamber. The asymmetric behaviors, such as single channel rectification, voltage-dependent gating and oriented incorporation into the membrane, must be correlated to the molecular structure of polytheonamide B.View full abstractDownload PDF (2234K) -
Koichi SATO, Kikuko HORIBE, Minori SAITO-MITSUI, Masatoshi HORI, Shige ...1997 Volume 110 Issue supplement Pages 199-204
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe effects of discodermin A, an antimicrobial peptide extracted from sea sponge Discodermia kiiensis, on cell membranes were investigated using vascular smooth muscle cells and erythrocytes. At lower concentrations (0.1-3 μM), discodermin A increased muscle tension with an increase in intracellular free Ca2+ concentration ([Ca2+]i) indicated by the fluorescence of Ca2+ indicator, fura-PE3, in rat aortic smooth muscle. On the other hand, the higher concentration of discodermin A (10 - 30 μM) accelerated the leakage of loaded fura-PE3 from cells. In rabbit mesenteric artery treaded with discodermin A, addition of micromolar concentration of Ca2+ evoked contraction in the presence of ATP, suggesting that permeability of the membrane to Ca2+ and ATP is increased by discodermin A. Confocal fluorescence microscopy showed that discodermin A permeabilized the plasma membrane of A10 cells to fluorescent agents EthD-1 and the intracellular esterase coupled with another fluorescent agent calcein. Discodermin A also showed a hemolytic effect on rabbit erythrocytes, suggesting that discodermin A permitted transmembrane passage of hemoglobin. These results suggest that discodermin A form pores of different sizes on the cytoplasm membrane in concentration- and time-dependent manners. Discodermin A may be a saponin-like bioactive peptide.View full abstractDownload PDF (4397K)
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