Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells
Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells
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DOI：
10.1016/s0014-2999(96)00500-6
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发表时间：
1996-10-24
影响因子：
5
通讯作者：
Inoue, K
中科院分区：
文献类型：
--
作者：
Ito, K;Nakazawa, K;Inoue, K
抗精神病药物抑制电压门控L型钙通道的特点是在大鼠神经元细胞系嗜铬细胞瘤PC 12细胞。氟哌啶醇和氯丙嗪（1-100 μ M）抑制Ca ~（2+）通道的Ba ~（2+）电流。氟匹立林和匹莫齐特在较低浓度下抑制Ba 2+电流（氟匹立林，0.1 pM至1 nM;匹莫齐特10 pM至1 μ M）。多巴胺受体拮抗剂和钙调蛋白拮抗剂的作用进行了测试，因为抗精神病药物是已知的，表现出这些药理活性。多巴胺D-2受体拮抗剂舒必利（1和10 μ M）和多巴胺D-2受体拮抗剂SCH-23390（R（+）-7-氯-8-羟基-3-甲基-1-苯基-2，3，4，5-四氢-1H-3-苯并氮杂卓; 1和10 μ M）也抑制Ba 2+电流。对于钙调素拮抗剂，W-7（N-（6-氨基己基）-5-氯-1-萘磺酰胺; 10和100 μ M）以及calmidazolium（10 nM至1 μ M）可降低Ba 2+电流。当用GDP β S代替胞内溶液中的GTP时，氟哌啶醇或氟螺环对Ba 2+电流的抑制不受影响。通过与K+通道抑制的比较以及与治疗相关性的关系，讨论了Ca 2+通道抑制的这些特性。
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 mu M) 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 mu M). Effects of dopamine receptor antagonists and calmodulin antagonists were tested because antipsychotic drugs are known to exhibit these pharmacological activities. Sulpiride (1 and 10 mu M), an antagonist to dopamine D-2 receptors, and SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 1 and 10 mu M), an antagonist to dopamine D-2 receptors, also inhibited the Ba2+ current. As for calmodulin antagonists, W-7(N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; 10 and 100 mu M) as well as calmidazolium (10 nM to 1 mu M) reduced the Ba2+ current. The inhibition by haloperidol or fluspirilene of the Ba2+ current was not affected when GTP in intracellular solution was replaced with GDP beta S. These properties of the Ca2+ channel inhibition are discussed by comparing with those of the K+ channel inhibition and in relation to therapeutic relevance.