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Volume 78 (1998)
- Issue 4 Pages 399-
- Issue 3 Pages 245-
- Issue 2 Pages 113-
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Volume 78, Issue 2
Displaying 1-14 of 14 articles from this issue
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Review
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Maria P. Abbracchio, Geoffrey Burnstock1998 Volume 78 Issue 2 Pages 113-145
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSIn this review, after a summary of the history and current status of the receptors involved in purinergic signalling, we focus on the distribution and physiological roles of purines and pyrimidines in both short-term events such as neurotransmission, exocrine and endocrine secretion and regulation of immune cell function, and long-term events such as cell growth, differentiation and proliferation in development and regeneration. Finally, the protective roles of nucleosides and nucleotides in events such as cancer, ischemia, wound healing, drug toxicity, inflammation and pain are explored and some suggestions made for future developments in this rapidly expanding field, with particular emphasis on the involvement of selective agonists and antagonists for purinergic receptor subtypes in therapeutic strategies.View full abstractDownload PDF (5021K) -
Keiko Akagi, Ko Hasebe, Kazuo Watanabe, Taku Nagao, Tetsuro Urushidani1998 Volume 78 Issue 2 Pages 147-159
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSWe examined the validity of the high K+ condition, widely used as a model to investigate the mechanism of acid secretion, employing isolated rabbit gastric glands. When Na+ in the nutrient solution was replaced with K+, the acid secretion monitored by the accumulation of 14C-aminopyrine increased K+-concentration-dependently. Stimulation of carbachol or dbcAMP was also greatly enhanced by K+. The responses to forskolin, phorbol ester, gastrin and submaximal dose of histamine were potentiated in the high K+ condition, but the responses to isobutylmethylxanthine, calyculin A and the maximal dose of histamine were not. The augmented response to carbachol was not dependent on [Ca2+]o. Replacement of Na+ with any other ions, including Rb+, Cs+, Li+, tetramethylammonium and choline, increased the basal aminopyrine ratio. Most of these ions were also effective in enhancing the response to dbcAMP, but failed to augment the effect of carbachol. Replacement of Na+ with K+, Rb+, Cs+ and Li+ transiently elicited acid secretion in the isolated mouse whole stomach. These results suggest that the high K+ is not a simple model for the direct activation of the proton pump, but the augmentation consists of two components, i.e., the combined effects of low Na+ and high K+. The former augments basal and cAMP-stimulated acid production, whereas the latter augments acid production by any agonist except calyculin A.View full abstractDownload PDF (1652K) -
Kazuo Umemura, Shinji Kikuchi, Yasuhiro Suzuki, Mitsuyoshi Nakashima1998 Volume 78 Issue 2 Pages 161-167
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSTranilast, N-(3, 4-dimethoxycinnamoyl) anthranilic acid, a widely used antiallergy drug in Japan, has been shown to inhibit transforming growth factor-β1 release from fibroblasts and reduce collagen synthesis in keloid cells. In the present study, we have investigated the effect of this drug on cardiac hypertrophy in spontaneously hypertensive rats (SHR), with a focus on the cardiac collagen matrix, which is associated with myocardial stiffness. Twenty-four-week-old SHRs and Wistar Kyoto rats (WKYs) were administered tranilast (300 mg/kg) orally once a day for 4 weeks. This treatment significantly suppressed increases in left ventricular collagen concentration (P<0.05) and the left ventricular weight / body weights ratios (P<0.05) in SHRs, and tranilast was ineffective on collagen concentration and ventricular weight / body weights ratios in WKYs. Tranilast did not affect systolic or diastolic blood pressure, end-diastolic left ventricular pressure and heart rate in both SHRs and WKYs, and the agent did not change positive dp/dt or cardiac output in SHRs. The pressure-volume relationship curve was shifted to the left by the drug; the slope (k) of the logarithm of the pressure-volume relationship curve was significantly increased (P<0.05) in SHRs. It is concluded that the suppression of increases in cardiac collagen and left ventricular mass by tranilast results in a corresponding prevention of cardiac stiffness as studied in the SHR.View full abstractDownload PDF (1066K) -
Hitoshi Mitsuzumi, Makoto Kusamiya, Takafumi Kurimoto, Itaru Yamamoto1998 Volume 78 Issue 2 Pages 169-179
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSTo gain a better understanding of the possible mechanisms by which a stable form of ascorbate, ascorbic acid 2-glucoside (AA-2G), as an ascorbate source, augments antibody responses, we examined whether AA-2G enhances the anti-sheep-red-blood-cell (SRBC) plaque-forming cell (PFC) responses elicited with distinct interleukins that provide signals for B-cell proliferation and differentiation in cultured murine T-cell-depleted splenocytes. The anti-SRBC PFC responses were markedly reduced by T-cell depletion; and additions of the concanavalin A-stimulated murine splenocytes supernatant (CAS) or interleukin (IL)-1β, IL-2, IL-5, IL-4 or IL-6 to the culture limitedly restored the immune responses. AA-2G synergistically stimulated the anti-SRBC PFC responses in the presence of IL-1β-, IL-2, IL-5 or CAS, IL-1β among these cytokines being most highly affected. However, it failed to enhance the PFC responses elicited by IL-4 or IL-6. Repeated additions of ascorbic acid (AsA) during experimental periods could also produced the enhancing effect, but a single addition of the vitamin did not, because of its instability in the medium. It was shown that exposure to IL-1β, IL-2 or IL-5 must be done at early times after antigen stimulation of the cells to support their optimal responses and that AsA exerted its effect on day 2 and day 3 after the start of culture. These results suggest that AsA may up-regulate the in vitro IgM antibody responses in a cytokine-dependent manner.View full abstractDownload PDF (1229K) -
Md. Amirul Islam, Hiroshi Nojima, Ikuko Kimura1998 Volume 78 Issue 2 Pages 181-190
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSSeveral lines of evidence suggest the molecular and functional entity of muscarinic M1 receptors in mammalian heart. We have reported that acetylcholine (ACh) reduces the maximum upstroke velocity of action potential (Vmax) through activation of muscarinic M1 receptors, which is followed by a muscarinic M2 receptor-mediated increase. The present study sought to determine whether activation of β-adrenergic receptors modulates the muscarinic M1 and M2 receptor-mediated effects on Vmax in isolated mouse right atria. Intracellular recordings of spontaneous action potential were done using the conventional glass microelectrode technique. Isoproterenol (3 nM) completely antagonized ACh (5 μM)-induced reduction in Vmax. The antagonism was accompanied by a subsequent increase in Vmax. Propranolol (0.3 μM) abolished the effects of isoproterenol on ACh-induced changes in Vmax. Isoproterenol antagonized McN-A-343 (4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride) (300 μM, a muscarinic M1 receptor agonist)-induced reduction in Vmax. Oxotremorine (0.03 μM), a muscarinic M2 receptor agonist, did not affect Vmax by itself, but significantly increased it in the presence of 3 nM isoproterenol. The effects of isoproterenol were mimicked by cholera toxin (100 nM, 1 hr), a Gs-protein activator, and forskolin (10 nM), a direct activator of adenylyl cyclase. H-89 (N-[2-(p-bromocinnamylamino)ethyl]5-isoquinolinesulphonamide, 1 μM), a selective protein kinase (PK)-A inhibitor, abolished the antagonism by isoproterenol of ACh-induced reduction in Vmax. The present results suggest that activation of the β-adrenergic-Gs-adenylyl cyclase system antagonizes ACh-induced reduction (muscarinic M1-mediated) and potentiates the subsequent increase (muscarinic M2 receptor-mediated) in Vmax. The β-adrenergic antagonism of ACh-induced reduction in Vmax may involve cross-talk between PK-A and PK-C signaling pathways.View full abstractDownload PDF (1249K) -
Kazuo Sato, Yuta Taniuchi, Tomihisa Kawasaki, Fukushi Hirayama, Hiroyu ...1998 Volume 78 Issue 2 Pages 191-197
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSThe anticoagulant and antithrombotic effects of YM-75466 (N-[4-[(1-acetimidoyl-4-piperidyl) oxy]phenyl]-N-[(7-amidino-2-naphthyl)methyl]sulfamoyl acetic acid monomethanesulfonate), a novel orallyactive factor Xa (FXa) inhibitor, and warfarin were compared in mice. Both agents were orally administered in all studies. In ex vivo studies, the peak effects of YM-75466 occurred 1 hr after administration while the peak of warfarin activity occurred 18 hr after administration. At each peak, both YM-75466 and warfarin prolonged coagulation time dose-dependently. The dose response curve of warfarin for prothrombin time was steeper than that of YM-75466. In a thromboplastin-induced thromboembolism model, administration of 30 mg/kg YM-75466 or 3 mg/kg warfarin significantly improved the lethality ratio. In blood loss studies, YM-75466 did not increase blood loss from the tail even at 30 mg/kg, while warfarin markedly increased blood loss at 3 mg/kg. Agents that interfere with warfarin action did not interfere with YM-75466 action. In conclusion, this study shows that YM-75466 has advantages over warfarin: i) rapid onset of anticoagulant activity, ii) wide therapeutic range, iii) little effect on bleeding and iv) lack of drug interaction with agents that interfere with warfarin. These results suggest that YM-75466 may be promising as a novel oral anticoagulant agent.View full abstractDownload PDF (717K) -
Isao Sumioka, Tatsuya Matsura, Shigeo Kasuga, Yoichi Itakura, Kazuo Ya ...1998 Volume 78 Issue 2 Pages 199-207
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSS-Allylmercaptocysteine (SAMC), one of the water-soluble organosulfur compounds in ethanol extracts of garlic (Allium sativum L.), has been shown to protect mice against acetaminophen (APAP)-induced liver injury. In this study, we examined the mechanisms underlying this hepatoprotection. SAMC (100 mg/kg, p.o.) given 2 and 24 hr before APAP administration (500 mg/kg, p.o.) suppressed the plasma alanine aminotransferase activity increases 3 to 12 hr after APAP administration significantly. The hepatic reduced glutathione levels of vehicle-pretreated mice decreased 1 to 6 hr after APAP administration, but SAMC pretreatment suppressed the reductions 1 to 6 hr after APAP administration significantly. These inhibitory effects of SAMC were dose-dependent (50 - 200 mg/kg) 6 hr after APAP administration. As SAMC pretreatment (50 - 200 mg/kg) suppressed hepatic cytochrome P450 2E1-dependent N-nitrosodimethylamine demethylase activity significantly in a dose-dependent manner, we suggest that one of its protective mechanisms is inhibition of cytochrome P450 2E1 activity. SAMC pretreatment also suppressed the increase in hepatic lipid peroxidation and the decrease in hepatic reduced coenzyme Q9 (CoQ9H2) levels 6 hr after APAP administration. The hepatic CoQ9H2 content of the SAMC pretreatment group was maintained at the normal level. Therefore, we suggest that another hepatoprotective mechanism of SAMC may be attributable to its antioxidant activity.View full abstractDownload PDF (1243K) -
Ken-ichi Otsuguro, Toshio Ohta, Shigeo Ito, Yoshikazu Nakazato1998 Volume 78 Issue 2 Pages 209-215
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSEffects of purinoceptor antagonists on the relaxant responses to adenine nucleotides were examined to characterize the subtypes of P2-receptor in rat gastric circular muscle. In tissues contracted by acetylcholine, a P2-receptor antagonist, suramin (100 μM), inhibited the relaxant responses to ATP, adenosine 5′-O-(2-thiodiphosphate) (ADPβS) and α, β-methylene ATP but not that to adenosine, while a P1-receptor antagonist, 8-phenyltheophylline (3 μM) did vice versa. The inhibitory effect of suramin was more potent for the relaxant responses to α, β-methylene ATP than those to ATP or ADPβS. Pyridoxal-phosphate-6-azophenyl-2′, 4′-disulphonic acid (PPADS) (3 - 30 μM) and 4, 4′-diisothiocyanatostilbene-2, 2′disulphonate (DIDS) (30 and 100 μM) inhibited the relaxation caused by α, β-methylene ATP but not by ATP, ADPβS or adenosine. These results suggest that ATP and ADPβS cause relaxation via the classical P2Y receptors resistant to PPADS and DIDS. In addition, α, β-methylene ATP causes relaxation via the distinct P2 receptors sensitive to PPADS and DIDS in rat gastric circular muscle.View full abstractDownload PDF (747K) -
Kazuhide Ayajiki, Tomio Okamura, Hideyuki Fujioka, Koichi Nakayama, Ku ...1998 Volume 78 Issue 2 Pages 217-223
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSIn isolated canine cerebral and cutaneous arteries and duodenum, effects of neosurugatoxin (NSTX) on the response to nicotine were compared. Nicotine-induced relaxations are mediated by nitric oxide (NO) from vasodilator nerves in cerebral arteries and by calcitonin gene-related peptide (CGRP) in cutaneous arteries treated with NO synthase inhibitors. Duodenal relaxation to nicotine is mediated by NO from inhibitory nerves. Cerebral arterial strips without endothelium responded to nicotine with relaxations that were inhibited by NSTX (3×10-10 to 3×10-9 M) concentration-dependently. Relaxations to nicotine of duodenal strips were attenuated by NSTX and abolished by tetrodotoxin, whereas those induced by K+ and electrical stimulation were not influenced. In cutaneous arteries treated with NG-nitro-L-arginine, nicotine-induced relaxations were attenuated by NSTX as low as 10-10 M, but unaffected by tetrodotoxin. The inhibitory potency of NSTX was in the order of cutaneous artery > duodenum > cerebral artery. It is concluded that NSTX selectively antagonizes actions on nicotinic receptors in nitroxidergic nerves of cerebral arteries, CGRP-mediated sensory nerves of cutaneous artery and ganglionic cells of the duodenum, but the affinity of this toxin to nicotinic receptors in sensory nerves is the highest.View full abstractDownload PDF (896K)
Short Communications
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Toshiki Takagi, Peter W. Tsao, Ryuichi Totsuka, Tatsuo Suzuki, Takashi ...1998 Volume 78 Issue 2 Pages 225-228
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSThis study demonstrated the decrease of bone mineral density (BMD) in the type II collagen (CII)-induced arthritis (CIA) model in rats and the relationship between BMD and paw edema and the effect of dexamethasone-21-phosphate (DEX). The paw swelling occurred on Day 10 and reached its peak on Day 18 after CII injection. BMD in the CII-injected group is lower than that in the control group. BMD in the proximal and distal regions of the femur largely decreased in comparison with that of the middle region. The oral administration of DEX (0.1 mg/kg) inhibited the swelling and decrease of BMD in all three regions of the femur.View full abstractDownload PDF (657K) -
Hisayoshi Fujita, Minoru Yoshiyama, Kazuhide Takeuchi, Takashi Omura, ...1998 Volume 78 Issue 2 Pages 229-232
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSThis study was designed to access the effect of a nonpeptide vasopressin V1-receptor antagonist, OPC-21268, and a vasopressin V2-receptor antagonist, OPC-31260, on hemodynamics in the early phase and the late phase after myocardial infarction in rats. In the early phase, OPC-21268 (30 mg/kg/day) or OPC-31260 (30 mg/kg/day) was orally administered from day 1 to days 5 after the operation; and hemodynamics were measured at day 5, in the late phase from 10 weeks to 11 weeks and measured at the end of 11 weeks. In the early phase, OPC-21268 reduced the left ventricular end-diastolic pressure (LVEDP) concomitantly with the reduction in systemic blood pressure, but did not change LVEDP in the late phase. OPC-31260 reduced LVEDP and central venous pressure in both phases. OPC-21268 improved hemodynamics only in the early phase and OPC-31260 improved it in both phases.View full abstractDownload PDF (559K) -
Toshihiro Okamoto, Tomio Yamakawa, Ken-Ichi Yamamura, Okio Hino1998 Volume 78 Issue 2 Pages 233-235
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSThe interferon-γ (IFN-γ) transgenic mouse develops chronic hepatitis. In the present study, lymphoid cell infiltration and expression of the Fas system were studied in the transgenic mouse liver. Morphological analysis showed the infiltration of lymphoid cells at the portal area and necro-inflammation piecemeal necrosis and the intralobular region. The polymerase chain reaction revealed induction of Fas antigen and Fas ligand mRNA expressions. The chronic hepatitis in this mouse reflects the profiles of human chronic hepatitis.View full abstractDownload PDF (532K) -
Yuji Wada, Toru Egashira, Fusako Takayama, Yasumitsu Yamanaka, Kaori T ...1998 Volume 78 Issue 2 Pages 237-240
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSTo study the circadian rhythm of the monoamine and metabolite contents, cerebrospinal fluid was taken from the cisterna magna through a polyethylene catheter tube every 4 hr in the conscious rat. Norepinephrine and 3-methoxy-4-hydroxy-phenylglycol were found to describe a rhythm with the maximal content occurring during the dark phase and the minimal content occurring during the light phase. Dopamine levels increased significantly during the light phase compared with the dark phase. These results, given that cerebrospinal fluid can be taken chronically from conscious rats, indicate that our present method may be suitable for estimating changes in brain monoamine and metabolite contents.View full abstractDownload PDF (498K)
Rapid Communication
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Masako Uchii, Miyuki Takashima, Tomomi Sugiyama, Nobuo Kosaka1998 Volume 78 Issue 2 Pages 241-243
Published: 1998
Released on J-STAGE: April 26, 2001
JOURNAL FREE ACCESSThe purpose of this study was to evaluate the effects of 3-[bis(4-hydrozuphenyl)methyl]-2-[4-(2-chlorophenyl)-piperazin-1-ylcarbonyl]-1-(2-dimethylaminoethyl) indole methanesulfonate (KW-8232), a novel anti-osteoporotic agent, on bone loss in neurectomized rats. We also investigated the effect of KW-8232 on bone resorption in this animal model. Male Sprague-Dawley rats underwent unilateral hind-limb immobilization by sciatic neurectomy. KW-8232 (3, 10 and 30 mg/kg, p.o.) was effective in inhibiting femoral bone loss. KW-8232 decreased urinary pyridinoline and deoxypyridinoline excretion. These results indicate that KW-8232 effectively prevents the bone loss due to immobilization.View full abstractDownload PDF (279K)
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