盐酸利托君对孕妇子宫平滑肌细胞钾离子通道的激活作用。

Activation of K+ channels by ritodrine hydrochloride in uterine smooth muscle cells from pregnant women.

作者信息

Hamada Y, Nakaya Y, Hamada S, Kamada M, Aono T

机构信息

Second Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.

出版信息

Eur J Pharmacol. 1994 Dec 15;288(1):45-51. doi: 10.1016/0922-4106(94)90008-6.

DOI:10.1016/0922-4106(94)90008-6

PMID:7705467

Abstract

This study investigated the mechanism of activation of K+ channels by ritodrine hydrochloride in human myometrial smooth muscle cells. The patch-clamp technique was used for recording single channel currents. Ritodrine (10(-5) M) activated two types of K+ channels in cultured uterine smooth muscle cells from pregnant women: the Ca(2+)-activated K+ (KCa) channel and the ATP-sensitive K+ (KATP) channel. Forskolin (10(-4) M), an activator of adenylate cyclase, and protein kinase A activated the KCa channel. In addition, 10(-4) M GTP activated the KCa channel in inside-out patches using a pipette containing 10(-5) M ritodrine. The KATP channel was activated by protein kinase A, but not by 10(-4) M GTP. The beta-adrenoceptor agonist ritodrine activates two types of K+ channels: the KCa channel via direct gating by GTP-binding proteins and possibly via cAMP-dependent phosphorylation, and the KATP channel possibly via cAMP-dependent phosphorylation. These mechanisms partially explain the relaxing effect of ritodrine hydrochloride.

摘要

本研究调查了盐酸利托君在人子宫肌层平滑肌细胞中激活钾通道的机制。采用膜片钳技术记录单通道电流。利托君（10⁻⁵ M）在来自孕妇的培养子宫平滑肌细胞中激活了两种类型的钾通道：钙激活钾（KCa）通道和ATP敏感性钾（KATP）通道。腺苷酸环化酶激活剂福斯可林（10⁻⁴ M）和蛋白激酶A激活了KCa通道。此外，使用含有10⁻⁵ M利托君的移液管，10⁻⁴ M GTP在膜内面向外的膜片中激活了KCa通道。KATP通道被蛋白激酶A激活，但未被10⁻⁴ M GTP激活。β肾上腺素能受体激动剂利托君激活两种类型的钾通道：通过GTP结合蛋白直接门控并可能通过cAMP依赖性磷酸化激活KCa通道，以及可能通过cAMP依赖性磷酸化激活KATP通道。这些机制部分解释了盐酸利托君的松弛作用。