Alpha 1-adrenergic and muscarinic cholinergic stimulation of phosphoinositide hydrolysis in adult rat cardiomyocytes.

作者：Joan Heller Brown, Iain L. O. Buxton, Laurence L. Brunton · 发表于：Circulation Research · 年份：1985 · DOI：10.1161/01.res.57.4.532 · 被引用次数：296 · 研究领域：Ion channel regulation and function、Cardiac electrophysiology and arrhythmias、Mitochondrial Function and Pathology

Cardiac alpha-adrenergic receptors mediate cellular responses to norepinephrine through an undefined series of molecular events. We examined the possibility that phosphoinositide hydrolysis was stimulated through alpha-adrenergic receptors in cardiomyocytes purified from adult rat ventricle. Phosphoinositide stores were labeled with [3H]inositol, and [3H]inositol phosphate formation was assessed after the addition of lithium chloride and norepinephrine. Norepinephrine increased the accumulation of [3H]inositol phosphate by approximately 5-fold, giving a maximal response at approximately 30 microM and a half-maximal response at approximately 1 microM. There was a significant increase in [3H]inositol phosphate formation in response to norepinephrine at 5 minutes, and the response was linear over 40 minutes. Norepinephrine-stimulated [3H]inositol phosphate formation was not blocked by propranolol (1 microM) or yohimbine (0.1 microM) but was completely antagonized by the alpha 1-selective antagonist prazosin (0.1 microM). Muscarinic cholinergic receptor activation by carbachol also stimulated [3H]inositol phosphate formation in rat ventricular myocytes. The maximal effect of carbachol (approximately 2-fold) was always less than that of norepinephrine. The combined effects of norepinephrine and carbachol were additive, suggesting that the two hormones do not share a common rate-limiting step. Removal of extracellular calcium and addition of ethylene glycol bis(beta-amino ether)-N,...