Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 105, Issue 6
Displaying 1-7 of 7 articles from this issue
  • Yasuo OGAWA, Takashi MURAYAMA
    1995 Volume 105 Issue 6 Pages 423-430
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Ryanodine receptor (RyR) is a calcium release channel protein on the intracellular Ca2+-store. While inositol 1, 4, 5-trisphosphate receptor (IP3R), another intracellular calcium release channel protein, is mainly found in non-muscle cells, such as neurons and hepatocytes, and smooth muscles, RyR is the Ca2+-release channel protein in skeletal and cardiac muscles. At least three genetically distinct isoforms of RyR are identified: isoform proteins Ryrl, Ryr2, and Ryr3 expressed by ryr1, ryr2 and ryr3, respectively. In the central nervous system where IP3R is much more abundant than RyR, the main isoform of RyR is Ryr2, which is specific to the cardiac ventricular muscle. Recently, ryr3 was detected in specific regions of the brain. In this paper, the heterogeneous distribution and localization of RyR isoforms in the brain are summarized. The discussion extends into their putative functions, especially potential involvement in neuronal plasticity.
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  • Shinichi HATTA, Hideyo OHSHIKA
    1995 Volume 105 Issue 6 Pages 431-436
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The mechanism whereby hormones or neurotransmitters activate G proteins and their intracellular effectors can be studied in reconstituted systems using purified components. However, the regulation of receptor-G protein signaling appears to be substantially more complex in the cell and several additional components participate in this event. To study the relationship among G proteins receptors, and effectors in complex systems, such as membranes of permeable cells, it is necessary to employ methods that selectively allow the examination of G protein activation. One such method is photoaffinity labeling using a hydrolysis-resistant, photoaffinity GTP analog, P3 (4-azidoanilido)-P1-guanosine 5'-triphosphate (AAGTP). Here we describe the synthesis and purification of [32P] AAGTP as well as a procedure suitable studying the G protein function in membrane preparations. Photoaffinity labeling in rat cerebral cortex membranes showed that at least four G proteins (GsH, GsL, Gi, and Go) were labeled by [32P] AAGTP. [32P] AAGTP labeling on Gs and Gi was altered in concert with the activation states of those G proteins. An agonistspecific increase in [32P] AAGTP labeling of the G protein α-subunit in a membrane preparation has also been demonstrated. Thus, the photoaffinity labeling method with [32P] AAGTP makes it possible to investigate the behavior of individual G proteins in complex systems such as membrane preparations.
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  • Toshihiro MATSUMURA, Hiroyasu FURUICHI, Junkichi IZUMI, Hiroshi SUDA, ...
    1995 Volume 105 Issue 6 Pages 437-446
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The anti-ischemic and anti-anoxic effects of efonidipine, a dihydropyridine calcium antagonist, were studied in several models for cerebral ischemia and anoxia in mice and rats, and the effects were compared with those of nicardipine and flunarizine. Both efonidipine and flunarizine showed protective effects in the models of KCN-induced anoxia and complete ischemia induced by decapitation in mice 6 hr after the treatment, while nicardipine did not show such a longlasting effect. Efonidipine (1 mg/kg, i.p.), but not nicardipine and flunarizine, prolonged the tolerance times in the asphyxic anoxia model. In mice, efonidipine (4 mg/kg, i.p.) significantly reduced the cumulative mortality rate after bilateral carotid artery ligation. The survival rates at 20 hr after bilateral carotid artery ligation were 33% in the group treated with efonidipine, significantly higher than that in the control group, 0%. On the other hand, the treatment with nicardipine or flunarizine did not increase the rates at 20 hr after the ligation. Moreover, efonidipine attenuated the disturbance of cerebral energy metabolism induced by decapitation in rats. These effects of efonidipine observed in this study were on the whole superior to those of the reference drugs, strongly suggesting the improving effect of efonidipine on cerebral ischemia and anoxia.
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  • Kiyoshi TAKASUNA, Yoshio KASAI, Yutaka KITANO, Kazuhiko MORI, Kohji KA ...
    1995 Volume 105 Issue 6 Pages 447-460
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    We investigated the mechanisms of CPT-11-induced diarrhea. 1) CPT-11 (80 mg/kg, i.v.) induced watery diarrhea within 1 hr after dosing in saline-loaded (10 ml/kg, p.o.) rats. This was partially inhibited by subcutaneous injection of atropine (1 mg/kg) or ondansetron (1 mg/kg) and almost completely inhibited by a combination of atropine and ondansetron or by clonidine (0.3 mg/kg) or morphine (10 mg/kg) alone. 2) CPT-11 at the same dose reduced intestinal fluid absorption, which was blocked by the anti-diarrheal agents mentioned above. Intraluminal injection of CPT-11 (20 mg/2 ml) inhibited fluid absorption and induced fluid secretion. 3) CPT-11, 60 mg/kg, by single intravenous injection induced fewer enzymological and histological changes in the small intestine than 5-FU at 270 mg/kg, while 4 consecutive dosings of CPT-11 induced delayed diarrhea (days 5-7) associated with disruption of intestinal integrity. Co-administration with antidiarrheal agents, except for ondansetron, protected against watery diarrhea appearing within 1 hr after CPT-11 on days 3 and 4, but worsened delayed diarrhea. These results suggest that single injection of higher doses of CPT-11 causes watery diarrhea at an acute phase at least partly by reducing fluid absorption or increasing secretion, and that while conventional anti-diarrheal agents protect against watery diarrhea, their co-administration in repeated CPT-11 administration has no ameliorative effect on CPT-11 -induced delayed diarrhea.
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  • Ken-ichi KATAYAMA, Yasunori MORIO, Keiichiro HAGA, Takemi FUKUDA
    1995 Volume 105 Issue 6 Pages 461-468
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The affinity of cisapride for 5-HT4 receptors was investigated in comparison with those of other 5-HT4 receptor agonists and antagonists, such as 5-HT, 5-MeOT, mosapride, zacopride, metoclopramide, BIMU8, GR113808, SDZ 205-557 and ICS 205-930. Cisapride and the other compounds dose-dependently inhibited specific 3H-GR 113808 binding to 5-HT4 receptors in guinea pig striatal membranes, and complete inhibition of specific 3H-GR1 13808 binding was achieved at the high concentrations of these compounds. Cisapride was 1.9-, 7.3-, 4.3-, 11 and 26-fold more potent than 5-HT, 5-MeOT, mosapride, zacopride and metoclopramide, respectively, in competing for 5-HT4 receptors. To determine the manner of interaction between cisapride and 5-HT4 receptors, Scatchard analysis of 3H-GR113808 specific binding to striatal membranes was performed. Cisapride increased the Kd value of 3H-GR 113808 in striatal membranes in a dose-dependent manner without any influence on the binding density (Bmax) of 3H-GR1 13808. These findings indicate that cisapride binds to 5-HT4 receptors competing with 3H-GR 113808 in guinea pig striatal membranes.
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  • Koji ITO, Satsuki MAEDA, Kosuke TAKATORI, Kumeji TAKEUCHI
    1995 Volume 105 Issue 6 Pages 469-478
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Glyteer (GL) possessed a broad antimicrobial spectra against bacteria and fungi. The antimicrobial activity of GL was bactericidal action, but not bacteriostatic action. GL was more effective against fungi than bacteria. GL ointment also showed antimicrobial activity equal to that of GL. Furthermore, GL had an effect on methicillin-resistant Staphylococcus aureus (MRSA). Resistance to GL was not induced in broth cultures of Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, and Trichophyton mentagrophytes. These results suggest that GL applied externally exerts a potent effect as an anti-microbial drug for dermopathy with various microbialpathogens.
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  • Noriyasu NISHIMURA, Hideshi TAKASE, Tominori MORITA
    1995 Volume 105 Issue 6 Pages 479-489
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    To compare the effects of an angiotensin II (Ang II)-receptor antagonist and an angiotensinconverting enzyme (ACE) inhibitor on myocardial, vascular structure and reactivity, SHR (5week-old) were treated with losartan of captoril for 16 weeks. Losartan (10 mg/kg/day, p.o.) and captopril (30 mg/kg/day, p.o.) significantly prevented the development of hypertension with aging, and the effects by these drugs were almost similar. Losartan and captopril significantly reduced the ventricular weight and the thickening of the coronary artery. Maximal coronary flow (MCF) induced by adenosine in the isolated heart was significantly higher in both the losartan and captopril groups. However, MCF in the captopril group was significantly lower than that in the losartan group. The pressor response to exogenous norepinephrine in the mesenteric arterial bed was significantly lower in the losartan group, whereas that in the captopril group was not. These findings suggest that the local Ang II produced by enzymes other than ACE also may play a role in vascular hypertrophy and hyperresponsiveness in SHR.
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