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Increased Number of ß-Adrenoceptors in Hepatocytes from Rats Treated with 2-Acetylaminofluorene¹

Department of Pharmacology, University of Oslo, P. O. Box 1057, Blindern, 0316 Oslo 3, Norway

Treatment of rats with chemical carcinogens, including 2-acetylaminofluorene (2-AAF), leads to a strong increase in the hepatic catecholamine-sensitive adenylate cyclase activity. The present study was undertaken to investigate the mechanism for the development of this increase. We report that hepatocytes isolated from rats which had been fed 2-AAF (0.025% w/w) for 8–12 weeks had an increased number of ß-adrenoceptors, as determined by [³H]dihydroalprenolol binding to whole cells and [¹²⁵I]iodocyanopindolol binding to washed particles. For both ligands the number of binding sites was about 4-fold higher in hepatocytes from 2-AAF-treated rats than in those from controls. The adenylate cyclase activity of the carcinogen-fed animals showed both a general increase manifested in the basal level (2-fold) and in the activities obtained by stimulation with guanine nucleotides (2-3-fold), cholera toxin (1.5-fold), and glucagon (1.3-fold) and a selective, larger increase in the ß-adrenoceptor-linked activity (7-fold increment of the isoproterenol-sensitive activity). The results indicate that the number of hepatocyte ß-adrenoceptors increases during 2-AAF carcinogenesis. This may, at least in part, explain the rise in catecholamine-sensitive adenylate cyclase activity.

¹ This work was supported by grants from the Norwegian Cancer Society (Landsforeningen Mot Kreft) and the Norwegian Society for Fighting Cancer (Norsk Forening til Kreftens Bekjempelse).

² Research fellow of The Norwegian Cancer Society. To whom requests for reprints should be addressed.

³ Present address: Department of Pharmacology, Institute of Medical Biology, University of Tromsø, 9000 Tromsø, Norway.

Received 7/16/85. Revised 1/ 2/86. Accepted 1/10/86.