Ramagopal M V, Rash V A, Mustafa S J
Department of Pharmacology, School of Medicine, East Carolina University, Greenville 27858-4354.
Arch Int Pharmacodyn Ther. 1988 Sep-Oct;295:174-80.
Adenosine plays an important role in the regulation of coronary blood flow, as it relaxes the coronary smooth muscle through A2 receptors. Methylxanthines have been used to antagonize the A1 and A2 adenosine receptors in various tissues. The aim of the present study was to investigate the antagonistic profile of methylxanthines towards A2 adenosine receptor in bovine coronary arteries. 8-p-sulpho-phenyltheophylline (8-SPT), 1,3-diethyl-8-phenyl xanthine (DPX) and 8-phenyltheophylline (8-PT) shifted the concentration-response curve for NECA to the right in parallel. Enprofylline (EN) did not shift significantly the concentration-response for NECA to the right. 1,3-Dipropyl-8-(2-amino-4-chloro) phenylxanthine (PACPX) shifted the concentration-response curve for NECA to the right and showed a probable noncompetitive antagonism. Based on the KB values, the relative order of potency for the methylxanthine analogs were 8-SPT greater than DPX greater than PACPX greater than 8-PT greater than EN. The data suggest that 8-ST and DPX are potent A2 adenosine receptor antagonists.
腺苷在冠状动脉血流调节中发挥重要作用，因为它通过A2受体使冠状动脉平滑肌松弛。甲基黄嘌呤已被用于拮抗各种组织中的A1和A2腺苷受体。本研究的目的是研究甲基黄嘌呤对牛冠状动脉A2腺苷受体的拮抗作用特征。8 - 对磺基苯基茶碱（8 - SPT）、1,3 - 二乙基 - 8 - 苯基黄嘌呤（DPX）和8 - 苯基茶碱（8 - PT）使NECA的浓度 - 反应曲线平行右移。恩丙茶碱（EN）未使NECA的浓度 - 反应曲线显著右移。1,3 - 二丙基 - 8 - （2 - 氨基 - 4 - 氯）苯基黄嘌呤（PACPX）使NECA的浓度 - 反应曲线右移，并显示出可能的非竞争性拮抗作用。根据平衡解离常数（KB）值，甲基黄嘌呤类似物的效价相对顺序为8 - SPT大于DPX大于PACPX大于8 - PT大于EN。数据表明8 - ST和DPX是强效的A2腺苷受体拮抗剂。
