Newman W H, Becker B F, Heier M, Nees S, Gerlach E
Department of Pharmacology, Medical University of South Carolina, Charleston 29425.
Pflugers Arch. 1988 Nov;413(1):1-7. doi: 10.1007/BF00581221.
Adenosine, applied to the coronary system of guinea pigs at up to 10(-6) M, elicits dilatation solely via an endothelium-mediated process. We investigated the role of coronary A2 receptors in this dilation, since the coronary endothelium possesses adenosine A2-receptors with a stimulatory action on the adenylate cyclase. In situ, A2 receptor stimulation can be assessed by prelabeling the coronary endothelial adenine nucleotide pool with 3H-adenosine and subsequently determining the rate of release of radiolabeled cAMP induced by A2 agonists. Thus, perfusion of isolated hearts with 5'-N-ethylcarboxamidoadenosine (NECA) dose-dependently increased coronary flow and the release of 3H-cAMP from the endothelium. In the presence of 50 microM 2',5'-dideoxyadenosine (ddA), a P-site agonist which inhibits the catalytic activity of adenylate cyclase, coronary flow increases induced by both adenosine and NECA were unaffected. In contrast, ddA reduced the release of labeled cAMP in response to NECA by about 60%. In cultured endothelial cells, ddA likewise inhibited cAMP accumulation due to NECA by about 70%. Moreover, ddA antagonized the adenylate cyclase mediated flow response due to the PGI2 analogue, iloprost, as well as the positive chronotropic and inotropic actions of isoproterenol. The dissociation elicited by ddA between the coronary flow response and the release of cAMP strongly indicates that the endothelial A2 receptors which are linked to adenylate cyclase are not causally involved in endothelium-dependent coronary dilatation induced by adenosine.
腺苷以高达10⁻⁶ M的浓度作用于豚鼠冠状动脉系统时，仅通过内皮介导的过程引起血管舒张。我们研究了冠状动脉A2受体在这种舒张中的作用，因为冠状动脉内皮细胞具有腺苷A2受体，对腺苷酸环化酶有刺激作用。在原位，A2受体刺激可通过用³H-腺苷预标记冠状动脉内皮腺嘌呤核苷酸池，随后测定A2激动剂诱导的放射性标记cAMP的释放速率来评估。因此，用5'-N-乙基羧基酰胺腺苷（NECA）灌注离体心脏，剂量依赖性地增加冠状动脉血流量和内皮细胞中³H-cAMP的释放。在存在50 microM 2',5'-二脱氧腺苷（ddA）（一种抑制腺苷酸环化酶催化活性的P位点激动剂）的情况下，腺苷和NECA诱导的冠状动脉血流量增加不受影响。相反，ddA使NECA诱导的标记cAMP释放减少约60%。在培养的内皮细胞中，ddA同样使NECA引起的cAMP积累减少约70%。此外，ddA拮抗了前列环素类似物伊洛前列素介导的腺苷酸环化酶流量反应以及异丙肾上腺素的正性变时和变力作用。ddA引起的冠状动脉流量反应与cAMP释放之间的解离强烈表明，与腺苷酸环化酶相连的内皮A2受体与腺苷诱导的内皮依赖性冠状动脉舒张没有因果关系。
