Sabouni M H, Hussain T, Cushing D J, Mustafa S J
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4354.
J Cardiovasc Pharmacol. 1991 Nov;18(5):696-702. doi: 10.1097/00005344-199111000-00007.
The coupling of the human coronary adenosine receptor to a G protein was investigated in vitro. Hearts were obtained from accidental death victims and the left anterior descending coronary artery (LAD) was taken for experimentation. Cholera toxin (CT) and pertussis toxin (PT) ADP-ribosylated proteins with Mr of 45, 49 (CT), and 41 (PT) kDa. Both processes were sensitive to GTP gamma S. In LAD rings contracted with KCl, adenosine (ADO) and its analogs 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) produced concentration-dependent relaxation. These concentration-response curves were shifted to the right significantly in the presence of the competitive ADO receptor antagonist, 8-phenyltheophylline (8-PT), indicating the involvement of ADO receptors. Treatment with NaF/AlCl3, which uncouples G protein-mediated responses, caused significant attenuation of the relaxation responses to ADO, NECA, and CAD. When the rings were incubated with CT, there was an attenuation of the relaxations produced by ADO, CAD, NECA, and isoproterenol (ISOP). Incubation with PT resulted in significant inhibition of the relaxations induced by ADO, NECA, and CAD. The results provide evidence for the presence of CT- and PT-sensitive G protein(s) subserving the relaxing adenosine receptors in human coronary artery.
在体外研究了人冠状动脉腺苷受体与G蛋白的偶联。心脏取自意外死亡受害者，取左前降支冠状动脉（LAD）进行实验。霍乱毒素（CT）和百日咳毒素（PT）对分子量为45、49（CT）和41（PT）kDa的蛋白质进行ADP核糖基化。这两个过程均对GTPγS敏感。在与氯化钾收缩的LAD环中，腺苷（ADO）及其类似物5'-N-乙基羧酰胺腺苷（NECA）和2-氯腺苷（CAD）产生浓度依赖性舒张。在竞争性ADO受体拮抗剂8-苯基茶碱（8-PT）存在下，这些浓度-反应曲线显著右移，表明ADO受体参与其中。用NaF/AlCl3处理可使G蛋白介导的反应解偶联，导致对ADO、NECA和CAD的舒张反应显著减弱。当环与CT孵育时，ADO、CAD、NECA和异丙肾上腺素（ISOP）产生的舒张减弱。与PT孵育导致对ADO、NECA和CAD诱导的舒张有显著抑制作用。结果提供了证据，表明存在对CT和PT敏感的G蛋白，其参与人冠状动脉中舒张腺苷受体的作用。
