Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 93, Issue 6
Displaying 1-4 of 4 articles from this issue
  • [in Japanese]
    1989 Volume 93 Issue 6 Pages 315-320
    Published: 1989
    Released on J-STAGE: February 20, 2007
    JOURNAL FREE ACCESS
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  • Yasuyuki NOMURA
    1989 Volume 93 Issue 6 Pages 321-331
    Published: 1989
    Released on J-STAGE: February 20, 2007
    JOURNAL FREE ACCESS
    Important findings on the molecular and regulatory properties of neurotransmitter receptors, GTP-proteins, ion channels and protein kinases were briefly reviewed. On the basis of recent advances in the theme mentioned above, we investigated the transmembrane signalling mechanism of serotonin (5-HT)-evoked inward current responses under the voltage clamp condition (holding at -60 mV) in Xenopus oocytes injected with rat brain poly(A)+ mRNA, suggesting that 5-HT evokes a Cl- current via such a mechanism as follows: 1) activation of 5-HT1C subtype of receptors, 2) activation of pertussis toxin-sensitive Gi; Go, 3) phospholipase C activation, 4) inositol 1, 4, 5-trisphosphate (IP3) formation, 5) an increase of [Ca2+]i liberated by IP3, and 6) gating of Cl channels stimulated perhaps by Ca2+-calmodulin. On the other hand, protein kinase C (C-kinase) activation by diacylglycerol and Ca2+ seems to cause a feedback inhibition to the 5-HT responses by phosphorylation of certain proteins. Voltage-operated Ca channels of the N-type reconstituted in oocytes injected with brain mRNA seem to be modulated by C-kinase as well as by cAMPdependent protein kinase. Significances of oocytes using as a model system to analyze the molecular mechanism of neuronal signalling in the brain were stressed and reviewed.
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  • Hiroyuki MIZUNO, Nobuo KAWABATA, Hiromitsu OHNO, Miwa MISAWA
    1989 Volume 93 Issue 6 Pages 333-340
    Published: 1989
    Released on J-STAGE: February 20, 2007
    JOURNAL FREE ACCESS
    Effects of flutropium bromide, a new antiasthma drug possessing the quarternary ammonium structure of atropine derivatives, were investigated on the bronchodilatory activity with repeated inhalations in guinea pigs and on the hepatic drug metabolizing enzyme activities with repeated i.v. administration in rats. Single inhalation of flutropium bromide (0.03%) inhibited the ACh-induced bronchoconstriction without changing the fall in blood pressure induced by ACh. Flutropium bromide (0.03%) was inhaled for 5 min a day by placing the animal in an inhalation box, successively during periods of 14 and 28 days. The bronchodilatory effect of flutropium bromide after 14- or 28-day repeated inhalations was almost the same potency as that after single inhalation. Twenty-eight-day repeated inhalations did not change the body weight curve in guinea pigs; and in addition, 14-day repeated i.v. administration did not change the hepatic drug metabolizing enzyme activities in rats. From the above results, it is indicated that flutropium bromide causes neither reduction in response nor cumulative effect after repeated inhalations, and that the agent maintains the bronchodilatory effect without change in the hepatic drug metabolizing enzyme activities.
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  • Kazuo KAMEI, Sonoko TSUCHIDA, Masaru NISHIKIBE
    1989 Volume 93 Issue 6 Pages 341-347
    Published: 1989
    Released on J-STAGE: February 20, 2007
    JOURNAL FREE ACCESS
    Effects of NB-818, a new Ca2+ entry blocker, on a transient cerebral ischemic model in Mongolian gerbils were examined. Following bilateral common carotid arteries occlusion of 20 min duration, all the control animals died within 24 hr after reperfusion. The administration of NB-818 at 0.1 mg/kg, i.p., 30 min after reperfusion significantly reduced the mortality rate to 65.0% (P<0.01) ; and 0.01 mg/kg, i.p., had a tendency to reduce the mortality rate. In the nimodipine-treated groups, a similar effect was observed, whereas nicardipine and flunarizine did not show clear beneficial effects in the ischemic model. Furthermore, the administration of NB-818 at 0.1 mg/kg, i.p., 15 min before occlusion also had a tendency to reduce the mortality rate. On the incidences of seizures induced by transient cerebral ischemia, there were no significant differences between each of the drugtreated groups and the control group. In NB-818 and nimodipine-treated groups, the morbidity scores decreased at 4 ?? 6 hr after reperfusion. In conclusion, the ameliorating effects of NB-818 and nimodipine in this severe cerebral ischemic model have advantages over those of nicardipine and flunarizine. Thus, these results suggest that NB-818 may be useful in the treatment of ischemic cerebral damage.
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