Increased number of beta-adrenoceptors in hepatocytes from rats treated with 2-acetylaminofluorene.
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 beta-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 beta-adrenoceptor-linked activity (7-fold increment of the isoproterenol-sensitive activity). The results indicate that the number of hepatocyte beta-adrenoceptors increases during 2-AAF carcinogenesis. This may, at least in part, explain the rise in catecholamine-sensitive adenylate cyclase activity.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D020120:Iodocyanopindolol; D008099:Liver / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D020120:Iodocyanopindolol; D015073:2-Acetylaminofluorene; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases