γ-氨基丁酸诱导的犬基底动脉收缩

Gamma-aminobutyric acid-induced contraction of the dog basilar artery.

作者信息

Suzuki Y, Okada T, Shibuya M, Kageyama N, Asano M, Hidaka H

出版信息

Pharmacology. 1984;29(1):24-30. doi: 10.1159/000137988.

Abstract

gamma-Aminobutyric acid (GABA) produced a biphasic action, that is, a relaxation followed by a contraction in the isolated dog basilar artery. Repeated applications of each concentration of GABA (10(-6), 10(-5), 10(-4), 10(-3) M) at regular intervals under resting conditions caused a stepwise increase in the contractile response. Marked reproducible contractile responses occurred (ED50: 1.3 X 10(-5) M), after at least 8-10 applications. The GABA-induced contraction as well as relaxation was blocked by bicuculline and picrotoxin. Pretreatment with inhibitors of prostaglandin synthesis such as aspirin (3 X 10(-6) to 3 X 10(-4) M) and indomethacin (3 X 10(-6) M) reduced the contractile response to GABA in an irreversible manner and without affecting the relaxation induced by GABA. These inhibitors increased the resting tone but reduced the tone in strips subjected to repeated applications of GABA. 15-Hydroperoxyarachidonic acid at concentrations of 1 X 10(-6) and 1 X 10(-5) M also attenuated the contractile response to GABA in a dose-dependent fashion. These observations suggest that GABA may modulate the contractile effect by inducing the production of contraction-causing prostaglandin(s) mediated through GABA receptors and/or by some as yet undefined mechanism.

摘要

γ-氨基丁酸（GABA）产生双相作用，即在离体犬基底动脉中先出现舒张，随后出现收缩。在静息条件下，每隔一定时间重复应用每种浓度的GABA（10⁻⁶、10⁻⁵、10⁻⁴、10⁻³M）会导致收缩反应逐步增强。在至少8至10次应用后，出现了明显可重复的收缩反应（半数有效剂量：1.3×10⁻⁵M）。GABA诱导的收缩以及舒张均被荷包牡丹碱和印防己毒素阻断。用前列腺素合成抑制剂如阿司匹林（3×10⁻⁶至3×10⁻⁴M）和吲哚美辛（3×10⁻⁶M）预处理以不可逆方式降低了对GABA的收缩反应，且不影响GABA诱导的舒张。这些抑制剂增加了静息张力，但降低了反复应用GABA的条带中的张力。浓度为1×10⁻⁶和1×10⁻⁵M的15-氢过氧花生四烯酸也以剂量依赖方式减弱了对GABA的收缩反应。这些观察结果表明，GABA可能通过诱导通过GABA受体介导的引起收缩的前列腺素生成和/或通过某种尚未明确的机制来调节收缩效应。