Kenakin T P, Beek D
J Pharmacol Exp Ther. 1984 May;229(2):340-5.
Both prenalterol and pirbuterol are partial agonists (when compared to isoproterenol) in rat left atria. Schild analysis with the beta-1 adrenoceptor selective antagonist atenolol indicated that all three agonists stimulate beta-1 adrenoceptors in this preparation. Atria from rats implanted with mini-osmotic pumps which delivered isoproterenol (400 micrograms kg-1 hr-1) s.c. for 4 days were 9 times less sensitive than control, to isoproterenol, and produced no responses to either prenalterol or pirbuterol. Schild analysis with atenolol on these desensitized atria indicated a homogeneous population of beta-1 adrenoceptors. In the desensitized atria, both prenalterol and pirbuterol functioned as competitive antagonists of responses to isoproterenol and Schild analysis yielded estimates of the equilibrium dissociation constants (Kp) of prenalterol (0.09 micron) and pirbuterol (2 micron) in these tissues. The estimates of Kp were utilized to calculate the relative efficacy of pirbuterol and prenalterol; pirbuterol was shown to have 2.3 times the efficacy of prenalterol on beta-1 adrenoceptors. The implications of this method as a means of calculating the Kp for partial agonists are discussed. These data also serve as a caveat to the use of pirbuterol in the determination of functional cardiac beta adrenoceptor subtypes in experimental animals and in man.
在大鼠左心房中，普瑞特罗和吡布特罗均为部分激动剂（与异丙肾上腺素相比）。使用β1肾上腺素能受体选择性拮抗剂阿替洛尔进行的希尔德分析表明，这三种激动剂在此制剂中均刺激β1肾上腺素能受体。给大鼠皮下植入微型渗透泵，持续4天给予异丙肾上腺素（400微克/千克·小时），其心房对异丙肾上腺素的敏感性比对照组低9倍，对普瑞特罗或吡布特罗均无反应。用阿替洛尔对这些脱敏心房进行希尔德分析表明，存在均匀的β1肾上腺素能受体群体。在脱敏心房中，普瑞特罗和吡布特罗均作为异丙肾上腺素反应的竞争性拮抗剂起作用，希尔德分析得出了这些组织中普瑞特罗（0.09微摩尔）和吡布特罗（2微摩尔）的平衡解离常数（Kp）估计值。利用Kp估计值计算了吡布特罗和普瑞特罗的相对效能；结果表明，吡布特罗对β1肾上腺素能受体的效能是普瑞特罗的2.3倍。讨论了该方法作为计算部分激动剂Kp的一种手段的意义。这些数据也警示了在实验动物和人类中使用吡布特罗来确定功能性心脏β肾上腺素能受体亚型的情况。
