Corr P B, Yamada K A, DaTorre S D
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
Basic Res Cardiol. 1990;85 Suppl 1:31-45. doi: 10.1007/978-3-662-11038-6_3.
The alpha 1-adrenergic receptor exists as at least two distinct subtypes, alpha 1a and alpha 1b. Based on hydrophobic exclusion studies and limited proteolysis of the cloned receptor, it appears to possess characteristics analogous to other membrane-bound receptors including seven membrane spanning domains, three extracellular, and three intracellular loops, with extensive glycosylation near the extracellular amino terminus. Although the receptor is coupled to phospholipase C in cardiac myocytes, with activation resulting in the production of inositol trisphosphate (IP3) and diacylglycerol, recent findings suggest that the receptor may also be linked to phospholipase A2, phospholipase D, and cyclic nucleotide phosphodiesterase. The alpha 1-adrenergic receptor has been shown to increase in response to myocardial ischemia in a number of different species and to mediate not only positive inotropic effects, but also to contribute substantially to arrhythmogenesis. The increase in alpha 1-adrenergic receptors can also occur in isolated adult ventricular myocytes in response to hypoxia, a mechanism which appears to be secondary to the sarcolemmal accumulation of long-chain acylcarnitines. This increase in alpha 1-adrenergic receptors in hypoxic myocytes is also linked to an enhanced increase in IP3 in response to receptor stimulation. These and other findings obtained in vivo during ischemia suggest that alpha 1-adrenergic mechanisms can become prominent in myocardium under pathophysiologic conditions in which a depressed contractile state exists and may therefore serve as a secondary inotropic system. However, the arrhythmogenic effects of stimulation of the alpha 1-adrenergic receptor in the ischemic heart in man may contribute substantially to arrhythmogenesis and, thereby, to the incidence of sudden cardiac death.
α1 - 肾上腺素能受体至少以两种不同的亚型存在，即α1a和α1b。基于对克隆受体的疏水排斥研究和有限蛋白酶解，它似乎具有与其他膜结合受体类似的特征，包括七个跨膜结构域、三个细胞外环和三个细胞内环，在细胞外氨基末端附近有广泛的糖基化。尽管该受体在心肌细胞中与磷脂酶C偶联，激活后会产生肌醇三磷酸（IP3）和二酰基甘油，但最近的研究结果表明，该受体也可能与磷脂酶A2、磷脂酶D和环核苷酸磷酸二酯酶相关联。在许多不同物种中，α1 - 肾上腺素能受体已被证明会因心肌缺血而增加，并且不仅介导正性肌力作用，还在很大程度上促成心律失常的发生。α1 - 肾上腺素能受体的增加也可在离体成年心室肌细胞中因缺氧而出现，这一机制似乎继发于长链酰基肉碱在肌膜的蓄积。缺氧心肌细胞中α1 - 肾上腺素能受体的这种增加还与受体刺激后IP3的增强增加有关。这些以及在缺血期间体内获得的其他研究结果表明，在存在收缩状态抑制的病理生理条件下，α1 - 肾上腺素能机制在心肌中可能变得突出，因此可能作为一种继发性肌力系统。然而，在人类缺血心脏中刺激α1 - 肾上腺素能受体的致心律失常作用可能在很大程度上促成心律失常的发生，进而导致心脏性猝死的发生率增加。
