Leung E, Johnston C I, Woodcock E A
J Cardiovasc Pharmacol. 1986 Sep-Oct;8(5):1003-8. doi: 10.1097/00005344-198609000-00018.
Stable analogues of adenosine were used to investigate the specificity of the receptors mediating its negative chronotropic and inotropic responses in isolated guinea-pig atria. The order of potencies for both responses was NECA = L-PIA = CHA = 2-chloroadenosine much greater than D-PIA. These analogues also inhibited adenylate cyclase in atrial and ventricular membranes, the order of potency being L-PIA = CHA = NECA much greater than D-PIA. The methylxanthines 8-phenyltheophylline, 1,3-diethyl-8-phenylxanthine and isobutylmethylxanthine antagonized both the pharmacologic responses of these agonists and their effect on adenylate cyclase. Antagonism produced by the methylxanthines was competitive as indicated by linear Schild plots for all three antagonists. The affinity constants obtained for the chronotropic and inotropic responses were similar to those obtained for adenylate cyclase inhibition. These results suggest that the negative inotropic and chronotropic effects of adenosine are mediated by RI adenosine receptors coupled to inhibition of adenylate cyclase.
使用腺苷的稳定类似物来研究介导其对离体豚鼠心房负性变时性和变力性反应的受体的特异性。两种反应的效价顺序为NECA = L-PIA = CHA = 2-氯腺苷远大于D-PIA。这些类似物还抑制心房和心室膜中的腺苷酸环化酶，效价顺序为L-PIA = CHA = NECA远大于D-PIA。甲基黄嘌呤8-苯基茶碱、1,3-二乙基-8-苯基黄嘌呤和异丁基甲基黄嘌呤拮抗这些激动剂的药理反应及其对腺苷酸环化酶的作用。如所有三种拮抗剂的线性Schild图所示，甲基黄嘌呤产生的拮抗作用是竞争性的。从变时性和变力性反应获得的亲和常数与从腺苷酸环化酶抑制获得的亲和常数相似。这些结果表明，腺苷的负性变力性和变时性作用是由与腺苷酸环化酶抑制偶联的RI腺苷受体介导的。
