Brodde O E
Divison of Renal & Hypertensive Diseases, University of Essen, Federal Republic of Germany.
Am J Cardiol. 1988 Aug 11;62(5):24C-29C. doi: 10.1016/s0002-9149(88)80063-8.
Radioligand binding studies have demonstrated convincingly the coexistence of beta 1 and beta 2 adrenoceptors in the human heart. Both subtypes are involved in the increase in tissue levels of cyclic adenosine monophosphate in isolated, electrically driven, human right atria and in the activation of adenylate cyclase in human cardiac membrane preparations. In isolated, electrically driven strips of human right atria, isoproterenol increased contractile force through stimulation of both beta 1 and beta 2 adrenoceptors, while the selective beta 2-adrenoceptor agonist, procaterol, caused its positive inotropic effect predominantly through beta 2-adrenoceptor stimulation. Norepinephrine, however, increased contractile force solely via beta 1-adrenoceptor stimulation. In this preparation, dobutamine also acted as a full agonist, producing a positive inotropic effect through stimulation of both beta-adrenoceptor subtypes. Dopexamine hydrochloride, on the other hand, having an approximately 10-fold greater affinity for right atrial beta 2 than for beta 1 adrenoceptors, acted as a partial agonist (maximal positive inotropic effect: about 30% that of isoproterenol). Similar effects have been obtained in human right and left ventricular strips; thus, there can be no doubt that cardiac beta 2 adrenoceptors can contribute to the positive inotropic effects of beta-adrenoceptor agonists in the human heart. Besides mediating positive inotropic effects, right atrial beta 2 adrenoceptors may be involved in the regulation of heart rate since, in healthy volunteers, the selective beta 2-adrenoceptor antagonist, ICI 118,551, was more potent than the selective beta 1-adrenoceptor antagonist, bisoprolol, in antagonizing isoproterenol-induced tachycardia, when both antagonists were administered in doses that selectively occupied more than 90% of beta 2 and beta 1 adrenoceptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
放射性配体结合研究令人信服地证明了人类心脏中β1和β2肾上腺素能受体共存。两种亚型均参与了在分离的、电驱动的人右心房中，环磷酸腺苷组织水平的升高以及人心肌膜制剂中腺苷酸环化酶的激活。在分离的、电驱动的人右心房条带中，异丙肾上腺素通过刺激β1和β2肾上腺素能受体增加收缩力，而选择性β2肾上腺素能受体激动剂丙卡特罗主要通过刺激β2肾上腺素能受体产生其正性肌力作用。然而，去甲肾上腺素仅通过刺激β1肾上腺素能受体增加收缩力。在该制剂中，多巴酚丁胺也作为完全激动剂，通过刺激两种β肾上腺素能受体亚型产生正性肌力作用。另一方面，盐酸多培沙明对右心房β2的亲和力比对β1肾上腺素能受体大约高10倍，它作为部分激动剂（最大正性肌力作用：约为异丙肾上腺素的30%）。在人右心室和左心室条带中也获得了类似的效果；因此，毫无疑问，心脏β2肾上腺素能受体可促成β肾上腺素能受体激动剂在人类心脏中的正性肌力作用。除了介导正性肌力作用外，右心房β2肾上腺素能受体可能参与心率调节，因为在健康志愿者中，当两种拮抗剂分别以选择性占据超过90%的β2和β1肾上腺素能受体的剂量给药时，选择性β2肾上腺素能受体拮抗剂ICI 118,551在拮抗异丙肾上腺素诱导的心动过速方面比选择性β1肾上腺素能受体拮抗剂比索洛尔更有效。（摘要截短于250字）
