The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 58, Issue 1
Displaying 1-11 of 11 articles from this issue
  • Feng-Nien Ko, Tian-Shung Wu, Sheng-Teh Lu, Yang-Chang Wu, Tur-Fu Huang ...
    1992 Volume 58 Issue 1 Pages 1-9
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    The pharmacological properties and mechanism of the action of protopine on isolated rat thoracic aorta were examined. It inhibited norepinephrine (NE, 3μM)-induced tonic contraction in rat thoracic aorta in a concentration-dependent manner (25-100 μg/ml). The phasic contraction caused by NE was inhibited only by a high concentration of protopine (100 μg/ml). At the plateau of NE-induced tonic contraction, the addition of protopine also caused relaxation. This relaxing effect of protopine was not antagonized by indomethacin (20 μM) or methylene blue (50 μM), and it still existed in denuded rat aorta or in the presence of nifedipine (2-100 μM). Protopine also inhibited high potassium (60 mM)-induced, calcium-dependent (0.03-3 mM) contraction of rat aorta in a concentration-dependent manner. Neither cAMP nor cGMP level was changed by protopine. Both the formation of inositol monophosphate caused by NE and the phasic contraction induced by caffeine were also not affected by protopine. 45Ca2+ influx caused by either NE or K+ was inhibited by protopine concentration-dependently. It is concluded that protopine relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.
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  • Hisashi Kuribara, Takayasu Asami, Iturou Ida, Sakutaro Tadokoro
    1992 Volume 58 Issue 1 Pages 11-18
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    Characteristics of the ambulation-increasing effect of MK-801, a non-competitive NMDA antagonist, were assessed through the coadministration of MK-801 with various central-acting drugs in mice. The MK-801 (0.3 mg/kg, i.p.)-induced ambulation-increment with a slight ataxia was maximum at around 50 min, and ambulation returned to the control level at about 3 hr after the administration. At 1 mg/kg, the mouse''s activity transiently increased, followed by a decrease due to a marked ataxia, which was due to neither stereotypy nor convulsion, for 20-50 min, and then increased again; the ambulation-increment continued even at 4 hr after the administration. Coadministration of MK-801 (0.3 mg/kg, i.p.) with either methamphetamine (2 mg/kg, s.c.), cocaine (20 mg/kg, s.c.), GBR-12909 (10 mg/kg, i.p.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) or morphine (10 mg/kg, s.c.) produced a significant enhancement of the effect. However, 0.1 mg/kg of MK-801 had no effect on the interaction with these drugs. On the other hand, the ambulation-increas ing effect of MK-801 (0.3 mg/kg) was significantly reduced by haloperidol (0.03 and 0.1 mg/kg, s.c.), ceruletide (0.01 and 0.1 mg/kg, i.p.), reserpine (0.05 and 2 mg/kg, s.c., pretreatment 4 hr before) and nimodipine (1 and 3 mg/kg, i.p.), but it was scarcely modified by α-methyl-p-tyrosine (100 and 200 mg/kg, i.p., pretreatment 24 hr and 4 hr before), imipramine (20 mg/kg, i.p.), 6R-L-erythro-5, 6, 7, 8-tetrahydro-biopterin (100 mg/kg, i.p.), pilocarpine (1 and 4 mg/kg, s.c.), N6-(L-2-phenylisopropyl)-adenosine (0.03 and 0.1 mg/kg, s.c.) and naloxone (1 and 5 mg/kg, s.c.). These results indicate the MR-801 increases the mouse''s ambulatory activity through stimulation of the dopaminergic system which is strongly affected by a calcium-dependent mechanism.
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  • Takehisa Iwama, Naoko Komatsu, Ken-ichi Shikada, Sakuya Tanaka
    1992 Volume 58 Issue 1 Pages 19-25
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    We performed an in vivo evaluation of bronchodilation using a model of antigen-induced bronchoconstriction in anesthetized guinea pigs pretreated with indomethacin, pyrilamine and propranolol, and the results were compared with those for the histamine-induced response. Test drugs were administered intravenously when the antigen or histamine response reached its peak. Leukotriene (LT) D4 antagonists, FPL55712 and LY171883, gradually reduced the antigen-induced response, whereas the lipoxygenase inhibitor phenidone had no such effect. The bronchodilator theophylline rapidly reduced the antigen-induced response, and the adenylate cyclase activator forskolin had a similar effect. The following drugs also had no effect: nifedipine (calcium-channel antagonist), cromakalim (potassium-channel opener), amlexanox and disodium cromoglycate: DSCG (anti-allergic drugs), OKY-046 (thromboxane A2 synthetase inhibitor), and dapsone (anti-inflammatory drug). Theophylline, the beta-adrenoceptor agonist salbutamol and the histamine H1-blocker pyrilamine had only a small reversing effect on histamine-induced bronchoconstriction. These results suggest that antigen-, but not histamine-, induced bronchoconstriction in anesthetized guinea pigs is a useful in vivo model for evaluating the bronchodilating effect of anti-asthmatic drugs.
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  • Tadashi Nagamatsu, Noriyuki Kojima, Nobuyuki Kondo, Tomohisa Hattori, ...
    1992 Volume 58 Issue 1 Pages 27-36
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    The suppressive effect of cyclosporin A (CyA) on the development of glomerulonephritis was evaluated in rats with either original- or crescentic-type anti-glomerular basement membrane (GBM) nephritis. CyA (2.5, 10 or 20 mg/kg) was given p.o. daily to original-type anti-GBM nephritic rats for 10 days from the day after the injection of anti-GBM serum. The development of the nephritis was dose-dependently suppressed by CyA before the production of specific antibody against rabbit γ-globulin (the heterologous phase). In addition, CyA suppressed glomerular infiltration of leukocyte subsets (leukocyte with common antigen, T cell, helper T cell, suppressor/cytotoxic T cell, macrophage/monocyte). CyA was given p.o. daily to crescentic-type anti-GBM nephritic rats for 10 days from the 10th day after the injection of anti-GBM serum. CyA-administration caused a distinct suppression of the deterioration of nephritis during the autologous phase. In addition, CyA markedly suppressed the antibody production. The above data indicate that CyA has a beneficial effect on anti-GBM nephritis, and the antinephritic action of this agent may be due to the inhibition of glomerular infiltration of leukocyte subsets as well as the suppression of the antibody production.
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  • Satomi Kitagawa, Yu Yamaguchi, Noriko Imaizumi, Masaru Kunitomo, Motoh ...
    1992 Volume 58 Issue 1 Pages 37-46
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    The present study was designed to delineate changes in serum lipid levels following various kinds of tissue injury or inflammation such as contact sensitivity to picryl chloride, thermal burn, carrageenin-induced edema, the administration of turpentine oil, Freund''s complete adjuvant (FCA), killed Bordetella pertussis (BP) or lipopolysaccharide (LPS). A uniform change in the serum lipid metabolism was observed in mice that received these inflammatory stimuli; that is, increases in total cholesterol, free cholesterol and phospholipid levels, a decrease in the ester ratio and a decline in lecithin: cholesterol acyltransferase activity as well as a decrease in albumin levels, which is an index of the acute-phase response. However, serum triglyceride levels were increased by treatment with the bacterial stimuli (FCA, BP and LPS) but decreased by treatment with the other stimuli. The serum free cholesterol and phospholipid levels were significantly correlated with the intensity of contact sensitivity, which was modified by treatment with cyclophosphamide. Indomethacin or dexamethasone suppressed carrageenin-induced edema and inhibited some of the alterations in lipid metabolism that developed during inflammation because each affected a part of the lipid metabolism. These findings suggest that, like the appearance of acute-phase proteins, the uniform change in serum lipid metabolism may be another sensitive index of the acute inflammatory response.
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  • Jun Tamaoki, Kiyoshi Takeyama, Atsushi Chiyotani, Noritaka Sakai, Taka ...
    1992 Volume 58 Issue 1 Pages 47-53
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    To study the effect of the Kampo drug Saiboku-to (TJ-96) on ion transport function of airway epithelial cells, we studied bioelectric properties of cultured tracheal epithelium from dogs under short-circuit conditions in vitro. Addition of TJ-96 (1 mg/ml) to the mucosal solution of the Ussing chamber increased the epithelial short-circuit current (SCC) from 6.5 ± 0.7 to 11.4 ± 1.6μA/cm2 (P < 0.001). This effect was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC50) being 70.5 ± 12.6% (P << 0.001) and 3 μg/ml, respectively; and there were corresponding increases in transepithelial potential difference and cell conductance. Submucosal addition of TJ-96 likewise increased SCC, although the magnitude of the response was smaller as compared with the response to the mucosal addition. The TJ-96-induced increase in SCC was not affected by diphenylamine-2-carboxylate or furosemide but abolished by amiloride. Intracellular cyclic AMP levels were dose-dependently increased by TJ-96. These results indicate that TJ-96 may selectively stimulate Na absorption across the tracheal epithelium, probably through intracellular accumulation of cyclic AMP.
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  • Noboru Fukuda, Yoichi Izumi, Masayoshi Soma, Yoshiyasu Watanabe, Masas ...
    1992 Volume 58 Issue 1 Pages 55-60
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    To evaluate the contribution of L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF) on vascular cyclic GMP formation, we examined the effects of L-NG-monomethyl arginine (L-NMMA), and analog of L-arginine, on basal and acetylcholine (ACh)-, sodium nitroprusside (SNP)- and atrial natriuretic peptide (ANP)-induced cyclic GMP formations in rat mesenteric arteries. The mesenteric arteries were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the arteries were collected before and after infusions of graded doses of ACh, SNP or ANP in the absence or presence of 100 μM L-NMMA, and the levels of cyclic GMP were measured. Basal and ACh-induced cyclic GMP formations in the mesenteric arteries were significantly inhibited in the presence of L-NMMA, whereas a concomitant infusion of 300 μM L-arginine restored the inhibition of basal as well as ACh-induced cyclic GMP formations. L-NMMA did not affect SNP- and ANP-stimulated cyclic GMP formations, respectively. These results suggest that L-arginine is necessary for not only the stimulated cyclic GMP formation but also the basal cyclic GMP formation in the mesenteric arteries, whereas the SNP- and ANP-stimulated cyclic GMP formations in the arteries are independent of L-arginine.
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  • Akikazu Fujita, Tadayoshi Takeuchi, Fumiaki Hata, Osamu Yagasaki
    1992 Volume 58 Issue 1 Pages 61-66
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    The hypogastric nerve to guinea pig vas deferens was stimulated pre- or post-ganglionically by adjusting the position of the suction electrode. Both stimulations induced a biphasic contraction consisting of a rapid transient phase and a delayed tonic phase. Indomethacin partially inhibited the contraction induced by pre-ganglionic stimulation, but did not inhibit that induced by post-ganglionic stimulation. Prostaglandin (PG) E2 counteracted the inhibitory effect of indomethacin. Mepacrine also inhibited the contraction induced by pre-ganglionic stimulation. Arachidonic acid and PGE2 both reversed the inhibition. The PGE2-receptor antagonist SC-19220 inhibited the contraction induced by pre-ganglionic, but not post-ganglionic nerve stimulation. These results suggested that endogenous PGE2 is important in neurotransmission in the pelvic ganglion of guinea pigs.
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  • Ichiro Hirotsu, Yoshiko Horikawa, Tetsuro Kihara, Takafumi Ishihara, T ...
    1992 Volume 58 Issue 1 Pages 67-73
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    The effects of peripheral administration of 6-(R)-5, 6, 7, 8-tetrahydro-L-erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, α-methyltyrosine (α-MT). A subcutaneous dose of 250 mg/kg of α-MT decreased markedly both ambulatory activity and cerebral contents of norepinephrine, dopamine and their metabolites in mice. An intraperitoneal dose of 100 mg/kg of R-THBP, which did not alter ambulatory activities in normal mice, improved the hypoactivity in α-MT-treated mice. Moreover, R-THBP at intraperitoneal doses of 60 and 100 mg/kg inhibited the impairment of cerebral catecholamine metabolism induced by α-MT in mice. We suggest that the reversal of the α-MT effects by R-THBP might be due to reactivation of tyrosine hydroxylase in the central nervous system.
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  • Junji Kinami, Ying-Li Qu, Hiroshi Tsuchihashi, Takafumi Nagatomo, Taka ...
    1992 Volume 58 Issue 1 Pages 75-78
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    The Ca2+-antagonistic effects of the 1, 4-dihydropyridine derivative (±)SM-6586 and its optical isomers were compared with those of its two derivatives ((±)SM-7297 and (±)SM-7548) and other Ca2+-antagonists using a radioligand binding assay. The Ca2+-antagonistic effects of the optical isomers of SM-6586 were in the order of (+) > (±) > (−)SM-6586 in both rat brain and heart. The pKi value of (+)SM-6586 was comparable to those of nimodipine, nicardipine, nifedipine and nitrendipine. The pA2 value for (+)SM-6586 was the highest among the SM-6586 isomers, thus suggesting that (+)SM-6586 has a potent Ca2+-antagonistic effect.
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  • Tomomi Shindou, Shuichi Koizumi, Yasufumi Kataoka, Shigenori Watanabe, ...
    1992 Volume 58 Issue 1 Pages 79-82
    Published: 1992
    Released on J-STAGE: May 17, 2006
    JOURNAL FREE ACCESS
    The effect of N-methyl-D-aspartate (NMDA) on KCl-evoked endogenous dopamine (DA) release from slices of rat globus pallidus (GP) was examined. NMDA inhibited the KCl-evoked DA release in a dose-dependent manner. This in hibition was blocked by CPP, an NMDA antagonist. Tetrodotoxin partially antagonized the effect of NMDA. The NMDA-induced inhibition was also partially antagonized by bicuculline methiodide and was mimicked by muscimol. These results strongly suggest that 1) an activation of NMDA receptors exerts an inhibitory effect on dopaminergic transmission in GP and 2) GABAergic transmission is involved in the effect of NMDA.
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