Functional beta(3)-adrenoceptor in the human heart
Functional beta(3)-adrenoceptor in the human heart
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DOI：
10.1172/jci118823
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发表时间：
1996-07-15
影响因子：
15.9
通讯作者：
LeMarec, H
中科院分区：
文献类型：
--
作者：
Gauthier, C;Tavernier, G;LeMarec, H
β（3）-肾上腺素能受体参与代谢、肠舒张和血管舒张，然而，它们在人类心脏中的存在和作用尚未被记录。我们研究了几种β-肾上腺素受体激动剂和拮抗剂对心室肌内膜活检的机械性能的影响。在β（1）和β（2）肾上腺素受体拮抗剂纳多洛尔存在下，异丙肾上腺素产生一致的负性肌力作用。β（3）-肾上腺素受体激动剂的作用也产生类似的负性肌力作用，其效力顺序为：BRL 37344 > SR 58611接近CL 316243 > CGP 12177，对BRL 37344降低心肌收缩力的量效曲线不被纳多洛尔预处理改变，但被布萘洛尔右移，一种非选择性β-肾上腺素受体拮抗剂。β（3）-肾上腺素能受体激动剂也可引起人动作电位振幅的降低和复极相的加速。用聚合酶链反应检测人心室中β（3）-肾上腺素能受体转录本。这些结果表明：（a）β（3）-肾上腺素受体存在于人心脏中并起作用;和（B）这些受体负责儿茶酚胺的意外负性肌力作用，并可能参与导致心力衰竭的病理生理学机制。
beta(3)-adrenoceptors are involved in metabolism, gut relaxation, and vascular vasodilation, However, their existence and role in the human heart have not been documented. We investigated the effects of several beta-adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a beta(1)- and beta(2)-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also resulted from the action of beta(3)-adrenoceptor agonists with an order of potency: BRL 37344 > SR 58611 approximate to CL 316243 > CGP 12177, The dose-response curve to BRL 37344-decreasing myocardial contractility was not modified by pretreatment with nadolol, but was shifted to the right by bupranolol, a nonselective beta-adrenoceptor antagonist. beta(3)-adrenoceptor agonists also induced a reduction in the amplitude and an acceleration in the repolarization phase of the human action potential, beta(3)-adrenoceptor transcripts were detected in human ventricle by a polymerase chain reaction assay. These results indicate that: (a) beta(3)-adrenoceptors are present and functional in the human heart; and (b) these receptors are responsible for the unexpected negative inotropic effects of catecholamines and may be involved in pathophysiological mechanisms leading to heart failure.