| Project/Area Number |
02670896
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
外科・放射線系歯学
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUMOTO Ken Osaka Univ. Dent. School., 2nd Dept Oral & Maxillofac Surg, Assist. Prof., 歯学部附属病院, 講師 (20127301)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Tetsuo Osaka Univ. Dent. School., 2nd Dept Oral & Maxillofac Surg, Resident, 歯学部附属病院, 医員
NAKAZAWA Mitsuhiro Osaka Univ. Dent. School., 2nd Dept Oral & Maxillofac Surg, Assistant, 歯学部附属病院, 助手 (70217701)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Morphine / Calcium Channel / Potassium Channel / GTP-binding Protein / モルヒネの作用機序 / カルシウム拮抗剤 / 培養神経芽細胞腫細胞 / Morphine / Calcium channel / GTP γS / tolerance / hippocampus |
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| Research Abstract |
In the present study, we examined the mechanism of the action of morphine and morphine tolerance focusing on calcium dynamics. In rat hippocampal electrophysiological study, morphine enhanced the field potentials evoked in CA1 pyramidal cells. GTPgammaS, the analogue of GTP which activates GTP-binding proteins, inhibited the effect of morphine dose-dependently. It was also observed that morphine converted the aff inity of ^3H-nitrendipine binding to calcium channels to a low affinity state in rat hippocampal membrane fractions. On the other hand, the binding of ^3H-nitrendipine to the cortical membrane fractions in rodents were enhanced about 30% following chronic treatment of morphine without the alteration of affinity. Intracerebroventricular treatment of pertussis toxin, in which inactivates GTP-binding proteins, showed the similar results to morphine tolerance. These results suggested that the enhancement of calcium influx which caused by the inactivation of GTP-binding proteins had the important role of the morphine tolerance.
In 1991, we examined the effects of morphine on the intracellular concentration of calcium ([Ca^<2+>]i) in Fura-2 loaded human neuroblastoma cell SH-SY5Y. It was observed that 10^<-6> - 10^<-4>M morphine inhibited dose-dependently the carbachol-induced increment of [Ca^<2+>]i. Nifedipine, a calcium channel blocker, also inhibited this increment of [Ca^<2+>]i. Furthermore, nifedipine showed the same effect to KCL-induced increase of [Ca^<2+>]i whereas morphine had no effect. These results showed that morphine inhibits calcium influx through K-channels in this neuroblastoma cell. In conclusion, (1)morphine decreased the affinity of calcium channels through K-channels therby inhibits calcium influx intonerve terminals. (2)Following chronic treatment of morphine, the regulation of calcium dynamics probably altered by inactivation of pertussis toxin-sensitive GTP-binding proteins.
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