European Journal of Pharmacology, 112 (1985) 393-397 393 Elsevier DIFFERENTIAL EFFECTS OF ADRENERGIC AGONISTS AND PHORBOL ESTERS ON THE eq-ADRENOCEPTORS OF HEPATOCYTES AND AORTA J. ADOLFO GARCIA-SAINZ a.., RAFAEL VILLALOBOS-MOLINA a, SILVIA CORVERA a, JUDITH HUERTA-BAHENA a, GOZOH TSUJIMOTO b and BRIAN B. HOFFMAN b Departamento de Bioenergbtica, Centro de Investigaciones en Fisiolog~a Celular, a Departamento de Bioqu'lmica, Facultad de Medicina, Universidad Nacional Autbnoma de Mbxico, Apartado Postal 70-600, 04510, Mbxico, D.E, and h Department of Medicine, Stanford University School of Medicine, Stanford California 94305 and/' V.A. Medical Center, Palo Alto, California 94304, U.S.A. Received 11 December 1984, revised MS received 22 February 1985 J.A. GARCIA-SAINZ, R. VILLALOBOS-MOLINA, S. CORVERA, J. HUERTA-BAHENA, G. TSUJIMOTO and B.B. HOFFMAN, Differential effects of adrenergic agonists and phorbol esters on the c~ l-adrenoceptors of hepatocytes and aorta, European J. Pharmacol. 112 (1985) 393-397. 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 al-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 phosphati- dylinositol labeling in hepatocytes but was without effect on the action of the amine in aorta. Our data suggest that stereochemical differences for al-adrenergic activation in liver and aorta may exist and indicate that the ability of phorbol esters to inhibit a~-adrenergic effects is not universal. cq-Adrenoceptors Phorbol esters Hepatocytes Aorta 1. Introduction a-Adrenergic receptors have been divided into two subtypes, i.e. cq and a 2, on the basis of their affinity for agonist and antagonists and their mechanisms of signal transduction (Berthelsen and Pettinger, 1977; Fain and Garcia-Shinz, 1980). However, there are some data suggesting that dif- ferences might exist among adrenoceptors of the same subtype (Langer and Shepperson, 1982). The aim of the present work was to compare two model systems, rat hepatocytes and rabbit aorta, whose a~-adrenoceptors have been characterized * To whom all correspondence should be addressed. pharmacologically (Hoffman et al., 1980; Tolbert et al., 1980; Docherty et al., 1981; Hoffman et al., 1981). In both models al-adrenergic activation produces marked increases in the labeling of phos- phatidylinositol (Tolbert et al., 1980; Villalobos- Molina et al., 1982). The study of the same effect in tissues as different as the liver and the aorta allows a much simpler comparison of potencies and activities of adrenergic agents. We have re- cently described the ability of phorbol esters to inhibit a~-adrenergic effects in hepatocytes (Corvera and Garcia-S~inz, 1984). In the experi- ments described here the effect of the active phorbol ester, phorbol 12-myristate 13 acetate (TPA) on the a~-adrenergic-mediated stimulation of phosphatidylinositol labeling was compared in both tissues. 0014-2999/85/$03.30 © 1985 Elsevier Science Publishers B.V.