García-Sáinz J A, Villalobos-Molina R, Corvera S, Huerta-Bahena J, Tsujimoto G, Hoffman B B
Eur J Pharmacol. 1985 Jun 19;112(3):393-7. doi: 10.1016/0014-2999(85)90786-1.
Epinephrine, norepinephrine and phenylephrine stimulate phosphatidylinositol labeling with [32P]Pi in both rat hepatocytes and rabbit aorta. Methoxamine was a full agonist for this effect in rabbit aorta whereas cirazoline and oxymetazoline were partial agonists. In contrast, these three agents (methoxamine, cirazoline and oxymetazoline) were unable to stimulate phosphatidylinositol labeling in rat hepatocytes. Furthermore, cirazoline and oxymetazoline were able to displace the dose-response curve to epinephrine in rat hepatocytes, i.e., they behaved as antagonists. Binding competition curves of these agents with labeled adrenergic ligands indicate that the affinity of alpha 1-adrenergic receptors in these two tissues (aorta and liver) for the different agents tested was very similar. In addition it was observed that phorbol myristate-acetate inhibited in a dose-dependent fashion the epinephrine-mediated stimulation of phosphatidylinositol labeling in hepatocytes but was without effect on the action of the amine in aorta. Our data suggest that stereochemical differences for alpha 1-adrenergic activation in liver and aorta may exist and indicate that the ability of phorbol esters to inhibit alpha 1-adrenergic effects is not universal.
肾上腺素、去甲肾上腺素和去氧肾上腺素在大鼠肝细胞和兔主动脉中均能刺激[32P]Pi对磷脂酰肌醇的标记。甲氧明对兔主动脉中的这种效应是完全激动剂，而可乐定和奥昔麻黄碱是部分激动剂。相比之下，这三种药物（甲氧明、可乐定和奥昔麻黄碱）在大鼠肝细胞中不能刺激磷脂酰肌醇标记。此外，可乐定和奥昔麻黄碱能够使大鼠肝细胞中肾上腺素的剂量反应曲线发生位移，即它们表现为拮抗剂。这些药物与标记的肾上腺素能配体的结合竞争曲线表明，这两种组织（主动脉和肝脏）中α1-肾上腺素能受体对所测试的不同药物的亲和力非常相似。此外，还观察到佛波醇肉豆蔻酸酯以剂量依赖性方式抑制肾上腺素介导的肝细胞中磷脂酰肌醇标记的刺激，但对主动脉中胺的作用没有影响。我们的数据表明，肝脏和主动脉中α1-肾上腺素能激活可能存在立体化学差异，并表明佛波醇酯抑制α1-肾上腺素能效应的能力并非普遍存在。
