DIFFERENTIAL MITOGENIC ACTIONS OF ALPHA(1)-ADRENERGIC AND BETA-ADRENERGIC AGONISTS ON RAT HEPATOCYTES

alpha(1)-Adrenergic receptor-mediated responses are overwhelming in ad ult rat hepatocytes. Inversely, beta-responses are predominant over al pha(1)-responses in the hepatocytes that have been cultured at a low c ell density (10(4) cells/cm(2)) for 24 h. The insulin-EGF-induced DNA synthesis in the beta-response-dominant hepatocytes was doubled by bet a-agonists or cAMP-generating agents added far behind (16-20 h) the ad dition of insulin/EGF; i.e., immediately before the entry into the S-p hase of the cell cycle. Agonists of alpha(1)-adrenergic or other Ca2+- mobilising receptors added to the alpha(1)-response-dominant hepatocyt es increased DNA synthesis only if they were added within 1-2 h after the addition of insulin/EGF, at the early stage of G1-phase. Agonists of ''non-dominant'' receptors were rather antagonistic to agonists of ''dominant'' receptors. Thus, agonists of alpha(1)-adrenergic land oth er Ca2+-mobilising) receptors and agonists of beta-adrenergic land oth er cAMP-generating) receptors acted as comitogens in their own particu lar manners in the presence of growth factors in hepatocytes in which the respective receptor functions were dominant. (C) 1998 Elsevier Sci ence Inc.