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Volume 44 (1987)
- Issue 4 Pages 373-
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Volume 44, Issue 1
Displaying 1-14 of 14 articles from this issue
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Syed S. HASAN, Anil K.S. KUSHWAHA1987 Volume 44 Issue 1 Pages 1-6
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe effect of chronic treatment with datura (seed) extract was studied to investigate its effect on the energy metabolism and peroxidative activities in the brain of rats. Datura treatment was found to cause an increase in the activity of brain lipid peroxidase and catalase, while it caused a decrease in the activity of fructose diphosphate aldolase and glucose 6-phosphate dehydrogenase enzyme. A marked reduction was noted in the protein, DNA and RNA contents of datura administered rats.View full abstractDownload PDF (256K) -
Susumu OKABE, Yasushi AKIMOTO, Hiroki MIYAKE, Junko IMADA1987 Volume 44 Issue 1 Pages 7-14
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe proton pump inhibitor NC-1300 has antisecretory and cytoprotective activities in rats. The compound is labile at an acidic pH and degrades into various products. We attempted to identify these products after treatment at different pHs in vitro using HPLC. We also examined whether (A) NC-1300 treated at acidic pHs loses its efficacy on gastric secretion and gastric lesions and (B) whether the degradation products of NC-1300 have pharmacological effects in rats. The acidic degradation products proved to be mainly NC-1300-sulfide and partly o-dimethylaminobenzylalcohol (o-DMABA) and benzimidazole (BI). NC-1300, pretreated at pH 1.0, 1.25 or 1.5 for 30 min and given p.o. at 30 mg/kg, significantly inhibited gastric acid secretion in pylorus ligated rats and prevented development of HCl•ethanol-induced gastric mucosal lesions. The degree of antisecretory and cytoprotective activities by NC-1300 treated at pH 1.5 was almost the same as that obtained by NC-1300 treated at pH 7.0. NC-1300-sulfide or mixtures of degradation products, with or without unchanged NC-1300, also significantly inhibited the gastric acid secretion and lesion formation. We conclude that while NC-1300 degrades at low pHs, the compound treated at such a low pH exerts pharmacological effects presumably by the unchanged form of NC-1300 and/or its degradation products.View full abstractDownload PDF (407K) -
Masaru KUNITOMO, Yu YAMAGUCHI, Yoshiko FUTAGAWA, Yoshiko HAMAGUCHI, Yo ...1987 Volume 44 Issue 1 Pages 15-22
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSDietary cholesterol suppressed adjuvant arthritis, a chronic inflammatory disease, in rats, but did not significantly affect carrageenin edema, an acute inflammation. When rats were fed a high-cholesterol diet beginning 10 days before injection of adjuvant, the development of the adjuvant-induced arthritis was greatly suppressed. Cholesterol feeding prevented hypertrophy of the adrenal gland in arthritic rats, but had little influence on the serum corticosterone level. A significant positive correlation was observed between the adrenal weight and the severity of the arthritis. These findings suggest that the effect of cholesterol feeding is not due to increased adrenal sterol synthesis. Dietary cholesterol also prevented hypertrophy of the spleen, but had no effect on atrophy of the thymus in adjuvant-treated rats. Cholesterol-fed rats showed a significant decrease in the serum lipid peroxide level and a significant increase in the serum copper level. Adjuvant treatment not only enhanced hypercholesterolemia produced by cholesterol feeding, but also the level of free cholesterol in serum. These results suggest that dietary cholesterol may exert some effect on the immune response through changes in spleen and liver functions.View full abstractDownload PDF (476K) -
Isao MATSUOKA, Kunio SAKURAI, Tomoyuki ONO, Hironori NAKANISHI1987 Volume 44 Issue 1 Pages 23-33
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe vasocontractile response to methylene blue (Meb) was investigated in isolated rabbit aorta. Meb (1-100 μM) induced a slowly developing contraction after a long latency in rabbit aortic strip. The maximal contraction was obtained by 50 μM Meb, which corresponded to 1 μM noradrenaline (NA)-induced contraction. Once the maximal contraction was induced by Meb, the strip completely lost the contractile response to a further application of Meb. The usual NA-induced contraction, however, could be observed in such a Mebinsensitive aortic strip. Meb-induced contractions were not affected by atropine, diphenhydramine, methysergide, indomethacin, nordihydroguaiaretic acid and removal of endothelial cells from the aortic strip, but they were abolished by prazosin. In aortic strips from rabbits pretreated with reserpine (3.0 mg/kg, i.m.) for a day, Meb failed to induce contraction. Meb evoked the [3H] release from [3H]NA-preloaded aortic strips. In high performance liquid chromatographic analysis, a considerable amount of NA was found in the bathing fluid of the aortic strip in the presence of Meb. In addition, Meb pretreatment inhibited [3H] NA uptake by the aortic strip and abolished the contractile response to an electrical stimulation of adrenergic nerve terminals. Although Meb decreased the basal level of cyclic GMP in the aortic strip, Meb-induced [3H]NA release from the aortic strip was not affected by 8-bromo cyclic GMP. These results suggest that Meb-induced contraction of rabbit aorta is due to the release of endogenous NA from its storage pools of intramural adrenergic nerves through an independent mechanism of its cyclic GMP lowering effect. In addition, incubation of aortic strips with Meb resulted in depleting the storage NA and blocking the nerve function, suggesting that Meb might be useful for a pharmacological tool as an adrenergic neuron blocking agent in vitro.View full abstractDownload PDF (650K) -
Jun-ichi IMAGAWA, Hiroyuki NABATA, Kazushige SAKAI1987 Volume 44 Issue 1 Pages 35-41
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe cardiovascular effects of a novel antihypertensive agent, SGB-1534, and its α1-adrenoceptor antagonism in the renal vasculature were investigated in anesthetized dogs and compared with those of prazosin. The doses ofSGB-1534 (1-100 μg/kg) and prazosin (3-300 μg/kg) were increased by afactor of about 3 and given i.v. in a cumulative way. SGB-1534 produced dose-dependent decreases in systemic (systolic, mean and diastolic) blood pressure (SBP), left ventricular (LV) systolic and end-diastolic pressure, and femoral vascular resistance, accompanied by no changes in heart rate (HR), LVdP/dt max and pressurerate product. Femoral blood flow tended to increase, but the change was not significant. Renal blood flow and the vascular resistance remained virtually unchanged.Similar results were obtained with prazosin for the cardiovascular parameters testedexcept diastolic SBP and femoral vascular resistance, in which no significant changes occurred. SGB-1534 and prazosin dose-dependently attenuated renal vasoconstrictor responses to a relatively selective α1-adrenoceptor agonist, phenylephrine (3 or 10 μg) given into the renal artery. When the doses that attenuated the vasoconstrictor response to phenylephrine by 50% were compared on a weight basis, α1-adrenoceptor antagonistic activity of SGB-1534 was approximately 25 times more potent than that of prazosin in the renal vasculature of dogs. Both α1-adrenoceptor antagonists showed a significant positive correlation between the systemic hypotensive effects and the α1-adrenoceptor antagonism in the renal vasculature.Thus, it seems that SGB-1534, like prazosin, has a balanced effect decreasing afterload as well as preload and that the hypotension is mainly due to the α1-adrenoceptor antagonism in the peripheral vasculatures.View full abstractDownload PDF (430K) -
Takuji MIZUI, Noriko SHIMONO, Masami DOTEUCHI1987 Volume 44 Issue 1 Pages 43-50
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe protective mechanism of polyamines against acidified ethanol induced gastric damage was studied. Their oral administration prevented the formation of gastric mucosal lesions induced by 90% ethanol in 150 mM HCl in a dose-dependent manner, with the order of the protective potency being spermine>spermidine>putrescine. The acidified ethanol-induced lesions were accompanied by a concomitant increase in gastric mucosal lipid peroxide levels, but spermine in a protective dose could prevent the increment of lipid peroxides. Polyamines, in a concentration-dependent fashion, inhibited the reduction of nitroblue tetrazolium by superoxide anion radicals generated in vitro in the xanthine-xanthine oxidase system and the lipid peroxidation in vitro induced by ferrous ion in the porcine gastric mucosal homogenate. The order of the superoxide scavenging potency and the inhibitory potency of iron-induced lipid peroxidation by polyamines corresponded to the order to the protective potency against acidified ethanol induced gastric lesions. The present results suggest that cytoprotection by poly amines may be responsible for their antiperoxidative activities.View full abstractDownload PDF (424K) -
Seiji ICHIDA, Masahiro MORIYAMA, Kazuo YOSHIOKA, Shunji ARIYOSHI1987 Volume 44 Issue 1 Pages 51-61
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe contractile responses of isolated uterine segments from 17β-estradiol-3-benzoate-treated ovariectomized rats to acetylcholine (ACh) and high KCI in Ca-depleted modified Locke-Ringer solution on addition of CaCl2 were used as indicators of Ca2+ influxes through ACh receptor- and voltage-operated Ca2+ channels, respectively. L-Methionine (L-Met) significantly enhanced these responses. The enhancement depended on the time of treatment with L-Met and concentration of L-Met. 3-Deazaadenosine (3-DAA) plus homocysteine thiolactone (HCTL), which inhibit S-adenosylmethionine-dependent methylation, caused dose-dependent inhibition of these contractile responses to ACh and high KCI. These inhibitory effects of 3-DAA plus HCTL were significantly attenuated in the presence of L-Met. Protein carboxylmethyltransferase and phospholipid methyltransferase activities were detected in the isolated uterine segment under conditions similar to those in which the contractile responses were observed. 3-DAA plus HCTL inhibited these enzyme activities. These findings suggest that S-adenosylmethionine-dependent methylations of protein and/or phospholipid in isolated uterine segment are involved in the contractile responses to ACh and high KCI in Ca-depleted modified Locke-Ringer solution on addition of CaCl2.View full abstractDownload PDF (622K) -
Kazuo WATANABE, Shingo YANO, Wen-Chuan LIN1987 Volume 44 Issue 1 Pages 63-69
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSEffects of some anesthetics (pentobarbital, thiopental, alpha-chloralose and urethane) on gastric acid secretion were studied in the continuously perfused stomach in rats. Under urethane anesthesia, pentobarbital, thiopental and alpha-chloralose showed a definite stimulation on gastric acid secretion. Pretreatment with atropine or hexamethonium abolished the pentobarbital-induced acid secretion. Pentobarbital and thiopental did not elicit acid secretion in bilateral truncal vagotomized rats. In spinal rats, pentobarbital also stimulated acid secretion, but urethane, which was subcutaneously administered, reduced spontaneous acid output. The present results indicated that some anesthetics could stimulate gastric secretion in the anesthetized rat in contrast to the previously described inhibitory effect in the Shay rat.View full abstractDownload PDF (372K) -
Kumi SUGIHARA, Sachiko NAKANO, Munekazu GEMBA1987 Volume 44 Issue 1 Pages 71-76
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSCisplatin (cis-diamminedichloroplatinum II), an antitumor agent with a dose-limiting adverse effect of nephrotoxicity, increased lipid peroxidation in a time and concentration-dependent manner in rat renal slices incubated in vitro. The addition of an antioxidant, N-N'-diphenyl-p-phenylenediamine (DPPD), to the incubation medium completely inhibited this increase. We also studied the in vitro effects of agents that modify cisplatin nephrotoxicity on lipid peroxidation in the slices caused by cisplatin. Mannitol, which protects against cisplatin nephrotoxicity, almost completely inhibited the increase in lipid peroxidation caused by cisplatin. Methionine, which potentiates cisplatin nephrotoxicity, made the slices more susceptible to peroxidation. The decrease with cisplatin in p-aminohippurate (PAH) accumulation in incubated kidney cortical slices, the accumulation being a representative biochemical process in the transport ability of renal cells, was partially inhibited when DPPD was in the medium. The results suggested that cisplatin directly affected renal tissues in which free radicals generated by cisplatin may interact with membrane lipids to cause the production of lipid peroxides that damage membrane function. Compounds that modify cisplatin nephrotoxity such as mannitol and methionine may act by affecting the production of renal lipid peroxides by cisplatin.View full abstractDownload PDF (387K) -
Atsufumi MANABE, Sadao NAKAYAMA, Koji SAKAMOTO1987 Volume 44 Issue 1 Pages 77-84
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe effect of essential oils, eugenol, thymol and menthol, on erythrocytes, hepatocytes, dipalmitoyl phosphatidylcholine (DPPC)-liposomes and surface tension were studied at various concentrations. Maximal inhibition of eugenol, thymol and menthol on the hypotonic hemolysis in rat erythrocytes were observed at a concentration of 2 mM, 1 mM and 1 mM, respectively. Eugenol at 4 mM and thymol at 2 mM caused an acceleration of hypotonic hemolysis. In isolated rat hepatocytes, thymol caused an increase in GOT leakage, but eugenol at 4 mM and menthol at 0.1 and 0.4 mM inhibited the GOT leakage. The leakage of GPT from hepatocytes was inhibited by eugenol at 0.1 mM and 0.4 to 4 mM and menthol at 0.1 to 0.6 mM. The inhibition of eugenol and menthol on the LDH leakage in hepatocytes were observed at a concentration of 0.001 to 4 mM and 0.1, 0.4 and 0.6 mM, respectively. Thymol caused no change in GPT and LDH leakage. Eugenol, thymol and menthol indicated a depression of surface tension at a concentration of 0.1 mM. The rank by order of surface activity was eugenol>thymol. Eugenol, thymol and menthol depressed the phase-transition temperature of DPPC-liposomes. The depression of phase-transition temperature by thymol was greater than that by eugenol and menthol. These results suggest the periapical tissue damage produced by essential oils may be related to membrane lysis and surface activity and that the their tissue penetration may be related to membrane affinity and lipid solubility.View full abstractDownload PDF (467K) -
Ikunobu MURAMATSU, Shigetada NAKANISHI, Motohatsu FUJIWARA1987 Volume 44 Issue 1 Pages 85-92
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThree mammalian tachykinins (substance P, neurokinin A and B) and two non-mammalian ones (eledoisin and physalaemin) produced potent contractions of the isolated rabbit iris sphincter muscle. The rank order of potencies was eledoisin > neurokinin B = physalaemin > substance P > neurokinin A. The maximum efficacy was much the same. The contractile responses to neurokinin A and eledoisin developed more rapidly than did those to the other tachykinins used and were selectively attenuated by [D-Arg1, D-Pro2, D-Trp7, 9, Leu11]-SP. Electrical transmural stimulation produced a contraction consisting of cholinergic and tachykininergic components The tachykininergic component was abolished by pretreatment with capsaicin or by trigeminal denervation (Fujiwara et al., 1984). [D-Arg1, D-Pro2, D-Trp7, 9, Leu11]-SP attenuated the tachykininergic component, but not the cholinergic one. KCI and capsaisin also produced a tachykininergic contraction which was inhibited by [D-Arg1, D-Pro2, D-Trp7, 9, Leu11]-SP. Calcitonin gene-related peptide affected neither the iris sphincter muscle nor the response to electrical transmural stimulation. These results suggest that the tachykininergic responses induced by electrical transmural stimulation, KCI and capsaicin are predominantly mediated by neurokinin A, probably released from the peripheral endings of trigeminal nerves.View full abstractDownload PDF (406K) -
Hiroyuki NABATA, Masako UCHINO, Akira OKAZAKI, Tamotsu YAMAZAKI, Kazus ...1987 Volume 44 Issue 1 Pages 93-96
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSFenflumizole (2-(2, 4-difluorophenyl)-4, 5-bis(4-methoxyphenyl) imidazole) was given to rats in a single oral dose of 30 mg/kg. The plasma concentration of fenflumizole reached a peak 2-3 hr after the dosing in non-fasted as well as fasted rats. Two metabolites (demethylation products) of fenflumizole were also detected in the plasma, but only in traces. Fenflumizole (30 and 100 mg/kg) and aspirin (100 mg/kg), given orally 2 hr prior to i.v. arachidonate (80 mg/kg), were effective in protecting the rats from death. Fenflumizole in single oral doses of 100 to 800 mg/kg dose-dependently developed erosions in the rat gastric mucosa, but was much less ulcerogenic than aspirin (3.12-200 mg/kg). Thus, fenflumizole seems to possess a potent antithrombotic activity and a relatively low gastro-ulcerogenicity in rats.View full abstractDownload PDF (224K) -
Hiroyuki NABATA, Masako UCHINO, Akira OKAZAKI, Kazushige SAKAI1987 Volume 44 Issue 1 Pages 97-100
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSFenflumizole (2-(2, 4-difluorophenyl)-4, 5-bis(4-methoxyphenyl) imidazole) was given to dogs in a single oral dose of 3 or 10 mg/kg. The plasma concentrations of fenflumizole and the two metabolites (mono and di-demethyl forms) attained to the peak level 1-2 hr after dosing of fenflumizole, returning to near the predose levels 8 hr after the dosing. Fenflumizole (10 mg/kg) given orally significantly inhibited collagen- and ADP-induced platelet aggregations ex vivo over 4 hr after the dosing. Fenflumizole effectively inhibited in vitro collagen-induced platelet aggregation, but failed to prevent ADP-induced aggregation. The mono-demethyl form of fenflumizole inhibited in vitro ADP- and collagen-induced aggregations, but the di-demethyl form was ineffective in inhibiting them.View full abstractDownload PDF (244K) -
Miwa MISAWA, Kiyoteru TAKENOUCHI, Masaru SATO, Saizo YANAURA1987 Volume 44 Issue 1 Pages 101-104
Published: 1987
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSEffects of chlorpheniramine and two antiallergic drugs on the active cutaneous anaphylaxis (ACA) reaction induced by intradermal injection of Ascaris suum antigen in naturally sensitized dogs were investigated. Chlorpheniramine (10 mg/kg, intraduodenally (i.d.)) almost abolished the ACA reaction. NCO-650 (100 mg/kg, i.d.) had no inhibitory effect, while tranilast (300 mg/kg, i.d.) showed a weak inhibitory effect. These findings show that (i) the ACA reaction is almost totally mediated by histamine and (ii) ACA reaction is considerably resistant to antiallergic drugs such as tranilast and NCO-650.View full abstractDownload PDF (238K)
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