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有机和无机钙通道阻滞剂对莫能菌素和藜芦碱在无细胞外钙情况下诱导的γ-氨基丁酸释放的影响。

Effect of organic and inorganic calcium channel blockers on gamma-amino-n-butyric acid release induced by monensin and veratrine in the absence of external calcium.

作者信息

Sitges M

机构信息

Departamento de Neuroquímica, Instituto Mexicano de Psiquiatría, México.

出版信息

J Neurochem. 1989 Aug;53(2):436-41. doi: 10.1111/j.1471-4159.1989.tb07353.x.

DOI:10.1111/j.1471-4159.1989.tb07353.x
PMID:2473167
Abstract

The effects of two organic Ca2+ antagonists (verapamil and nitrendipine) and of two inorganic Ca2+ channel blockers (Co2+ and ruthenium red) on the Na+-dependent release of gamma-amino-n-butyric acid (GABA) triggered by veratrine and monensin in the absence of external Ca2+ were studied in mouse brain synaptosomes. Ca2+-independent release of GABA stimulated by the Na+ channel activator veratrine was inhibited with micromolar concentrations of verapamil and nitrendipine. In contrast, GABA release induced by the Na+ ionophore monensin was insensitive to the organic Ca2+ antagonists. Verapamil also failed to modify A23187-stimulated release of GABA in the presence of Ca2+ but inhibited high K+-induced release of the transmitter. Co2+ partially diminished veratrine-induced release but did not change monensin-induced release. Releasing responses to monensin and veratrine were insensitive to ruthenium red, which inhibited the Ca2+-dependent component of GABA release evoked by high K+ depolarization. These data demonstrate that the mechanism of inducing GABA release is different for veratrine and monensin, as evidenced by their differing sensitivities to inhibition by Ca2+ channel antagonists and organic Ca2+ blockers. It is concluded that voltage-sensitive Ca2+ channels of the presynaptic membrane are not involved in the inhibitory action of Ca2+ antagonists on the Na+-dependent, Ca2+-independent mechanism of GABA release.

摘要

在小鼠脑突触体中研究了两种有机钙拮抗剂(维拉帕米和尼群地平)以及两种无机钙通道阻滞剂(Co2+和钌红)对藜芦碱和莫能菌素在无细胞外钙条件下触发的γ-氨基丁酸(GABA)钠依赖性释放的影响。微摩尔浓度的维拉帕米和尼群地平可抑制由钠通道激活剂藜芦碱刺激的GABA非钙依赖性释放。相反,由钠离子载体莫能菌素诱导的GABA释放对有机钙拮抗剂不敏感。在有钙存在的情况下,维拉帕米也不能改变A23187刺激的GABA释放,但可抑制高钾诱导的递质释放。Co2+部分减少藜芦碱诱导的释放,但不改变莫能菌素诱导的释放。对莫能菌素和藜芦碱的释放反应对钌红不敏感,钌红可抑制高钾去极化诱发的GABA释放的钙依赖性成分。这些数据表明,藜芦碱和莫能菌素诱导GABA释放的机制不同,这可通过它们对钙通道拮抗剂和有机钙阻滞剂抑制作用的不同敏感性得到证明。结论是,突触前膜的电压敏感性钙通道不参与钙拮抗剂对GABA释放的钠依赖性、非钙依赖性机制的抑制作用。

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