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Volume 62 (1993)
- Issue 4 Pages 331-
- Issue 3 Pages 215-
- Issue 2 Pages 123-
- Issue 1 Pages 1-
Volume 62, Issue 4
Displaying 1-15 of 15 articles from this issue
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Hitoshi Kontani, Masumi Ginkawa, Takeshi Sakai1993 Volume 62 Issue 4 Pages 331-338
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSIn supine anesthetized rats, two cannulae were inserted into a unilateral ureter near the kidney and urinary bladder, respectively. Fluid from a reservoir placed approximately 27 cm above the rat was infused into the ureter lumen through the cannula near the kidney, and the resulting peristaltic pressure signals were measured from the cannula near the bladder. When drugs acting on ion channels were applied from the ureter lumen and their effects on the peristaltic pressure signals were studied, the K+ channel opener BRL 38227 (1×10-4M and 1×10-3M) was found to decrease the frequency dose-dependently. However, the K+ channel blockers glibenclamide and 4-aminopyridine at 1×10-3M did not affect peristaltic movement. Nifedipine (1×10-5M and 1×10-4M) decreased the frequency of peristalsis, but the effect was weaker than that of BRL 38227. Lidocaine at very high concentration (1.5×10-2 and 1.5×10-1 M) decreased the amplitude and increased the frequency of the peristaltic signals. These results indicate that the K+ channel opener has the most inhibitory effect on ureteral peristaltic function.View full abstractDownload PDF (463K) -
Hidenori Yazawa, Emi Iida-Kubota, Kazuo Honda1993 Volume 62 Issue 4 Pages 339-343
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe characterized the angiotensin II (All) receptor in human aortic smooth muscle cells (HASMCs). This receptor binds [125I]Sar1, Ile8-angiotensin II with a high affinity of 0.20±0.04 nM and a low capacity of 5.3±0.4 fmol/mg protein (230±17 sites/cell). Based on the K1 values, the ranking order of [125I]Sar1, Ile8-AII binding inhibition was as follows: Sar1, Ile8AII > AII > Dup 753 > All > AI » PD 123319. The addition of AII to HASMCs induced a rapid, transient increase in intracellular free Ca2+ concentration followed by a lower, sustained phase. When extracellular Ca2+ was removed by adding 3 mM EGTA, this initial transient increase was not changed, but the sustained phase was abolished. These results revealed AII receptors in HASMCs to be of the type 1 receptor subtype, which induce Ca2+ mobilization mainly from intracellular Ca2+ stores.View full abstractDownload PDF (308K) -
Hiroyuki Ohta, Kinzo Matsumoto, Hiroshi Watanabe, Mineo Shimizu1993 Volume 62 Issue 4 Pages 345-349
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSPaeoniflorin, a major constituent of peony root, has been demonstrated to attenuate the radial maze performance deficit produced by scopolamine. In the present study, to investigate the possible involvement of β-adrenergic systems in the paeoniflorin antagonism of the scopolamine deficit, the effects of two β-adrenoceptor antagonists, propranolol and atenolol, on the paeoniflorin effect were examined in male Wistar rats. Paeoniflorin (1 mg/kg, p.o.) significantly attenuated the scopolamine HBr (0.3 mg/kg, i.p.)-induced deficit in the choice accuracy in radial maze performance without changing the running time prolonged by scopolamine. Neither D, L-propranolol HCl, a lipophilic β-antagonist, at 3 mg/kg, i.p. nor atenolol, a hydrophilic β1-antagonist that is known to hardly ever cross the blood-brain barrier, at 1 mg/kg, i.p. impaired maze performance by itself or aggravated the scopolamine-induced deficit in radial maze performance. Both antagonists, however, completely blocked the antagonizing effect of paeoniflorin on the scopolamine deficit. These data suggest that the β-adrenergic systems, especially peripheral β1-adrenergic systems, are involved in the antagonizing effect of paeoniflorin on the scopolamine deficit in radial maze performance in rats.View full abstractDownload PDF (377K) -
Shigekatsu Kohno, Naoki Tsuzuike, Hideki Yamamura, Takeshi Nabe, Michi ...1993 Volume 62 Issue 4 Pages 351-355
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe quality of the resting tonus in isolated human bronchi was investigated using a peptide leukotriene (p-LT) antagonist, a 5-lipoxygenase inhibitor and others. (E)-2, 2-Diethyl-3 [2-[2-(4-isopropyl)-thiazoyl]ethenyl]succinanilic acid sodium salt (MCI-826), a newly synthesized compound that is a highly selective antagonist to LTD4 and LTE4, markedly relaxed the isolated human bronchi at low concentrations. A selective and competitive arachidonate 5-lipoxygenase inhibitor, 2, 3, 5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1, 4-benzoquinone (AA-861), also potently lowered the tonus. In addition, a large amount of spontaneously formed p-LTs was detected in the isolated human bronchial tissue as well as the lung parenchymal tissue. The isolated human bronchi responded to indomethacin treatment with contractions and the acceleration of p-LT formation. Atropine, an anticholinergic; mepyramine, an antihistaminic; and OKY-046, a thromboxane synthetase inhibitor, all showed no effect on the resting tonus. Taking into consideration the high responsiveness of the human airway smooth muscle to p-LTs and the present results, which were different from those on isolated guinea pig tracheas, it is strongly suggested that the spontaneously formed p-LTs largely participate in the resting tonus of the majority of isolated human bronchi.View full abstractDownload PDF (376K) -
Hideki Ono, Chiharu Fukushima, Hideomi Fukuda1993 Volume 62 Issue 4 Pages 357-362
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSExperiments were performed on intact and spinalized rats anesthetized with urethane and α-chloralose. In intact rats, administration of tizanidine (0.1 mg/kg, i.v.) decreased the mono- (MSR) and polysynaptic reflex potentials (PSR). Blood pressure was initially elevated and then lowered by tizanidine. Although pretreatments with hexamethonium and phentolamine prevented the tizanidine-induced decrease in blood pressure, the depressant effects of tizanidine on the reflexes remained. The α2-antagonist idazoxan inhibited the tizanidine-induced decrease in spinal reflexes, suggesting that central α2-adrenoceptors are involved in the depression of the reflexes. In spinalized rats, tizanidine transiently increased the MSR and gradually decreased the PSR. Blood pressure was elevated transiently by tizanidine. Although the hypertensive effect of tizanidine was inhibited by phentolamine, the effect of tizanidine on the PSR did not change. Prazosin blocked the stimulatory effect of tizanidine on the MSR and caused a rapid decrease of the PSR, suggesting that spinal α1-adrenoceptors are involved in the enhancement of the reflexes. These results suggest that the depressant effects of tizanidine on spinal reflexes are due to the supraspinal and spinal effects of the drug, and not to changes in blood pressure.View full abstractDownload PDF (379K) -
Takaji Yamaguchi, Kazuyuki Aihara, Shin-ichi Yamada, Sen-ichi Narita, ...1993 Volume 62 Issue 4 Pages 363-371
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated the effects of the newly synthesized proton pump inhibitor TY-11345, (±)-2-[(4-methoxy-6, 7, 8, 9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl)sulfinyl]-]H-benzimidazole sodium salt, on gastric mucosal proton pump (H+/K+-ATPase) activity, gastric acid secretion and gastro-duodenal lesions in experimental animals. TY-11345 potently inhibited H+/K+-ATPase activity in isolated rabbit gastric mucosal microsomes; and the inhibitory effect was enhanced under weak acid conditions, the IC50 (concentrations that inhibit the enzyme activity by 50%) being 5.8 μM and 9.9 μM at pH 6.0 and pH 7.4, respectively. In Ghosh & Schild rats, intravenous injection of TY-11345 significantly inhibited gastric acid secretion stimulated by tetragastrin; the effect of TY-11345 was twice as potent as that of omeprazole. In pylorus ligated rats, TY-11345 inhibited basal gastric acid secretion by both the intraduodenal and oral routes, with ED50 values of 1.2 and 4.0 mg/kg, respectively. These effects were 9 and 5 times more potent than those of omeprazole, respectively. Moreover, the antisecretory effect of TY-11345 persisted for more than 24 hr in pylorus ligated rats. In experimental ulcer models, TY-11345 prevented the formation of water-immersion stress, ethanol or indomethacin-induced gastric lesions and mepirizole-induced duodenal lesions in rats. The antiulcer effects of TY-11345 were 3 to 15 times more potent than those of omeprazole. These results suggest that TY-11345 has potent antisecretory and antiulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells, so that TY-11345 should be useful for the clinical treatment of peptic ulcer diseases.View full abstractDownload PDF (648K) -
Jian Guo Song, Shigeyuki Nakano, Shigehiro Ohdo, Nobuya Ogawa1993 Volume 62 Issue 4 Pages 373-378
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe circadian rhythms of the toxicity and the pharmacokinetics of methotrexate (MTX), as well as the effects of manipulation of feeding schedule on the rhythms, were investigated in mice. Male ICR mice were housed under a standardized light-dark cycle (12:12) with food and water ad libitum (ALF) or under the time-restricted feeding (TRF) schedule (8 hr during the light phase) for 1 day or 14 days before the drug administration. The animals received MTX (100 mg/kg, i.p.) once daily for 7 days in the toxicity studies and a single dose of MTX (100 mg/kg, i.p.) for the kinetic studies. Under the ALF, a significant dosing time dependency was demonstrated for the toxicity of MTX with a longer survival time for the middark dosing and a shorter one for the midlight dosing. The MTX kinetics also showed a significant rhythm, with the highest clearance at middark and the lowest one at midlight. The rhythm in MTX kinetics well coincided with that in the toxicity of the drug. The TRF had a marked influence on the rhythms of MTX kinetics and toxicity. Thus, the timing of dosing is important in the kinetics and the toxicity of MTX in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing that of the MTX kinetics.View full abstractDownload PDF (470K) -
Takao Komabayashi, Masamichi Noguchi, Tetsuya Izawa, Kazuhiro Suda, Mi ...1993 Volume 62 Issue 4 Pages 379-385
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe kinetics and mechanism of sn-1, 2-diacylglycerol (DAG) formation induced by isoprenaline were studied in rat parotid acinar cells. DAG accumulation induced by 100 μM isoprenaline reached its maximum at 1 min, rapidly decreased (about 50%) at 5 min and then remained constant for 30 min. DAG accumulation 1 min after isoprenaline treatment was dose-dependent. Either propranolol or phentolamine inhibited isoprenaline-stimulated DAG accumulation in a dose-dependent manner. Addition of a vasoactive intestinal polypeptide, forskolin, or dibutyryl cyclic AMP had no effect on DAG accumulation. Isoprenaline did not cause the release of [3H]choline or [3H]ethanolamine metabolites into the medium. Based on the kinetics of DAG formation and [32P]phosphoinositide breakdown, we conclude that isoprenaline-induced DAG formation was mainly related to the hydrolysis of [32P]phosphatidylinositol 4, 5-bisphosphate ([32P]PIP2). These results suggest that the effect of isoprenaline on DAG formation is mediated by α1-adrenoceptor activation, that it is not related to the increase in cyclic AMP, and that it is closely related to PIP2 hydrolysis.View full abstractDownload PDF (497K) -
Naowarat Suthamnatpong, Tomofumi Maehara, Atsunori Kanada, Tadayoshi T ...1993 Volume 62 Issue 4 Pages 387-393
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe role of cyclic GMP (cGMP) in nonadrenergic, noncholinergic (NANC) relaxation of the longitudinal muscle of rat proximal and distal colon was examined. Electrical field stimulation (EFS) of preparations of longitudinal muscle from the proximal region significantly increased the cGMP content. Nitro-L-arginine inhibited this increase, and L-arginine reversed the inhibitory effect of nitro-L-arginine. Exogenously added nitric oxide (NO) and atrial natriuretic peptide (ANP) also increased the cGMP content of preparations of the proximal colon and induced muscle relaxation. From these and our previous findings suggesting an essential role of NO in NANC inhibition in the proximal colon, we conclude that the mechanism of NANC inhibition in the proximal region of rat colon involves NO and a cGMP generating system. In contrast, although exogenously added NO and ANP increased the cGMP content in the distal colon to the same extent as in the proximal colon, they did not induce any muscle relaxation. Vasoactive intestinal peptide (VIP), the most likely candidate as a NANC neurotransmitter in rat distal colon, did not increase the cGMP content in this region. Furthermore, no participation of NO in the NANC inhibitory response was observed in the distal region, but EFS increased the cGMP content significantly. Thus we conclude that relaxation of longitudinal smooth muscle in the distal portion of rat colon is not associated with a change in the cGMP content.View full abstractDownload PDF (464K) -
Yuji Iwanaga, Nagao Suzuki, Ken-ichi Kato, Tatsuya Kimura, Kouji Morik ...1993 Volume 62 Issue 4 Pages 395-401
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSStimulatory effects of HSR-803 on intestinal motor activity in vitro were studied in guinea pig ileum. HSR-803 (1×10-6-1×10-4M) increased the amplitude of longitudinal muscle contractions and increased the frequency of peristalsis in isolated segments of guinea pig ileum. The stimulatory effect in amplitude and not frequency was abolished by 1×10-6M atropine. In the Magnus method with ileal segments, HSR-803 (1×10-7-1×10-4M) produced contractions concentration-dependently, which were inhibited by atropine (1×10-8 and 3×10-8M) and 3×10-7M tetrodotoxin (TTX). In the [3H]-quinuclidinyl benzilate (QNB) binding experiment with ileal smooth muscle, HSR-803 had low affinity for acetylcholine (ACh) receptors (pKi=4.47±0.04). In addition, HSR-803 failed to increase the spontaneous release and the electrical stimulation-induced [3H]ACh release in ileal smooth muscle. On the other hand, HSR-803 (1×10-5 M) enhanced contractions induced by ACh, but had no effect on contractions induced by carbachol, which is not hydrolyzed by acetylcholinesterase (AChE). In conclusion, HSR-803 stimulated ileal motor activity. However, HSR-803 had low affinity for ACh receptors and had no influence on ACh release. It is likely that HSR-803 stimulated motor activity mainly due to prevention of ACh hydrolysis.View full abstractDownload PDF (559K) -
Akio Fujimura, Tsuyoshi Shiga, Toshiaki Sudoh, Kyo-ichi Ohashi, Akio E ...1993 Volume 62 Issue 4 Pages 403-405
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSInfluence of α-receptor blockade on the time-dependent change in the effect of furosemide (a loop diuretic agent) was examined. Furosemide (30 mg/kg) was given orally to the doxazosin (an α1-blocker)- or vehicle-treated rats at 12 AM or 12 PM. Urine volume and urinary excretions of sodium and furosemide for 8 hr were significantly greater at 12 AM than at 12 PM in the vehicle-treated animals. However, such time-dependent changes in these parameters disappeared in the doxazosin-treated rats. These results suggest that the α1-receptor-mediated stimuli are involved in the mechanism of the time-dependent change in the effect of furosemide.View full abstractDownload PDF (207K) -
Masaaki Ishikawa, Masayasu Ozaki, Yoshio Takayanagi, Ken-ichi Sasaki1993 Volume 62 Issue 4 Pages 407-410
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSRats were immunized by intraperitoneal injection of ovalbumin emulsified with Freund incomplete adjuvant, and then the effect of an intravenous challenge with ovalbumin on hepatic drug-metabolizing enzyme activities was examined. The cytochrome P-450 content and ethylmorphine N-demethylase, benzphetamine N-demethylase, arylhydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities significantly decreased in rats treated with ovalbumin compared with control groups treated with saline, whereas there was no significant reduction in cytochrome b5, NADPH-cytochrome c reductase and NADH-cytochrome c reductase.View full abstractDownload PDF (266K) -
Xiang-Qian Zhang, Yasuo Watanabe, Masatoshi Ohnishi, Tsuyoshi Baba, Ta ...1993 Volume 62 Issue 4 Pages 411-414
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe inhibitory effects of calcium antagonists on high-potassium or glutamate (Glu) enhanced intracellular calcium ion ([Ca2+]i) levels were studied in cultured cerebellar granule cells. Dosages between 0.5 and 10 μM of flunarizine, nicardipine, SM6586 and SM12565 reduced the rise in [Ca2+]i induced by 50 mM KCl in a dose-dependent manner, although diltiazem, verapamil and nifedipine showed less effects on such [Ca2+]i increases. SM6586, SM12565 and flunarizine at dosages below 10 μM each reduced the magnitude of the [Ca2+]i increase induced by 25 μM Glu, but the other examined calcium antagonists were less effective. These results suggest the dissimilar efficacy of calcium antagonists on the inhibition of [Ca2+]i levels increased by high-potassium and Glu.View full abstractDownload PDF (276K) -
Itaru Ohoi, Hiroko Tobari, Keita Nakamura1993 Volume 62 Issue 4 Pages 415-418
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSGeneration of oxygen-derived free radicals (oxy-radicals) in the stored rat heart was measured by chemiluminescence. Hearts subjected (ischemia) or not subjected (non-ischemia) to a 4-min regional ischemia were frozen in liquid nitrogen and stored until assayed. The frozen myocardium was ground and oxygenated by mixing it with phosphate-buffered saline (Po2: 194 mmHg) containing lucigenin. The chemiluminescence intensity of ischemic myocardium was larger than that of non-ischemic myocardium. Recombinant human superoxide dismutase significantly decreased these intensities. These results indicate that O2- is one of the major oxy-radical species in the rat heart and that the generation of oxyradicals is enhanced by regional ischemia for 4 min.View full abstractDownload PDF (239K) -
Yoshimi Maruoka, Yukihiro Ohno, Terufumi Kato, Akira Hirose, Tohru Tat ...1993 Volume 62 Issue 4 Pages 419-422
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effects of SM-9018, a potential atypical neuroleptic, on monoamine metabolism were studied in rats. SM-9018 dose-dependently increased the levels of 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the cerebral cortex and striatum without affecting the levels of 5-HT, norepinephrine and their metabolites. This action persisted for 8 hr with a maximum effect at 1-2 hr. The SM-9018-induced increase of dopamine (DA) turnover, as indexed by HVA/DA and DOPAC/DA ratios, was comparable in the cerebral cortex and striatum, whereas the typical neuroleptic haloperidol preferentially enhanced the striatal DA turnover. These findings suggest that SM-9018, unlike haloperidol, increases DA turnover to a similar extent both in the cerebral cortex and striatum.View full abstractDownload PDF (296K)
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