Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells

Kanako Ito, Ken Nakazawa, Schuichi Koizumi, Min Liu, Kouichi Takeuchi, Takao Hashimoto, Yasuo Ohno, Kazuhide Inoue

研究成果: Contribution to journalArticle査読

30 被引用数 (Scopus)


Inhibition by antipsychotic drugs of voltage-gated L-type Ca2+ channels was characterized in rat neuronal cell line pheochromocytoma PC12 cells. Under whole-cell voltage-clamp, haloperidol and chlorpromazine (1-100 μM) inhibited Ba2+ current permeating through Ca2+ channels. Fluspirilene and pimozide inhibited the Ba2+ current at lower concentrations (fluspirilene, 0.1 pM to 1 nM; pimozide 10 pM to 1 μM). Effects of dopamine receptor antagonists and calmodulin antagonists were tested because antipsychotic drugs are known to exhibit these pharmacological activities. Sulpiride (1 and 10 μM), an antagonist to dopamine D2 receptors, and SCH-23390 (R(±)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be nzazepine; 1 and 10 μM), an antagonist to dopamine D1 receptors, also inhibited the Ba2+ current. As for calmodulin antagonists, W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; 10 and 100 μM) as well as calmidazolium (10 nM to 1 μM) reduced the Ba2+ current. The inhibition by haloperidol or fluspirilene of the Ba2+ current was not affected when CTP in intracellular solution was replaced with GDPβS. These properties of the Ca2+ channel inhibition are discussed by comparing with those of the K+ channel inhibition and in relation to therapeutic relevance.

ジャーナルEuropean Journal of Pharmacology
出版ステータス出版済み - 10 24 1996

All Science Journal Classification (ASJC) codes

  • Pharmacology

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