1988 Fiscal Year Final Research Report Summary
The mechanism of hypersensitization in diabetic state of neuromuscular synapse to depolarizing blockers
| Project/Area Number |
62480118
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Toyama Medical & Pharmaceutical University |
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Principal Investigator |
KIMURA Masayasu Professor, Dept. of Chemical Pharmacol., 薬学部, 教授 (60019099)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Shinjiroh Research Assistant, Dept. of Chemical Pharmacol., 薬学部, 助手 (10186744)
KIMURA Ikuko Associate Prof., Dept. of Chemical Pharmacol., 薬学部, 助教授 (70019131)
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| Project Period (FY) |
1987 – 1988
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| Keywords | diabetic state / muscle cell membrane / intracellular Ca^<2+> mobilization / site of action of succinylcholine / potentiation mechanism of -eudesmol / diabetic state-induced modification of intracellular Ca^<2+> mobilization / 糖尿病態による細胞内Ca動員 / Ca誘発脱感作 |
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| Research Abstract |
The aim of this study was to investigate the diabetic state-induced potentiation of depolarizing inhibition by using the pharmacological prode found from traditional Sino-Japanese medicines. The following results were obtained from the last two years.
1. The diabetic state-induced modification of muscle cell membranes were to lower resting membrane potentials, to decrease membrane conductance and to inhibit Ca^<2+> influx.
2. The occurrence of diabetic state converted the mode of succinylcholine-binding action from positive to negative one. The distribution of Ca^<2+> was concentrated in muscle tissues. This evidence was supported by increasing activity of Ca^<2+>.
3. The new Ca^<2+> mobilization was observed by the treatment with anti-cholinesterase, and was not accompanied by contraction of muscles. The Ca^<2+> mobilization was inhibited by low concentrations of d-tubocurarine, but not by succinylcholine. The result of patch clamp experiments showed that succinylcholine-activated single channel condictance was inhibited by high concentrations of external Ca^<2+>.
4. -Eudesmol, the constituent of atractylodes lancea, potentiated succinylcholineinduced blocking effect of neuromuscular synapse. The synapse in diabetic state was inhibited more increasingly by -eudesmol.
From the above results, we concluded that diabetic state-induced potentiation to depolarizing blockers may be caused by Ca^<2+>-dependent desensitization of neuromuscular synapse.
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