Abstract
A 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) containing diet was given to 6 weeks old female Donryu rats, and the number of adrenoceptors and the response of adenylate cyclase in the hepatocytes were measured. The treatment with 3'-MeDAB Ied to rapid increases in [125I]-iodocyanopindolol ([125I] ICYP)- and [3H] clonidine-binding sites to hepatic membranes without significant changes in the Kd values. The number or β-adrenoceptors defined by [125I] ICYP binding sites was increased with a biphagic mode. The [3H] clonidine binding reached a peak 2 weeks after the start of the carcinogen diet and then began a slow descent. The α2-adrenoceptor was defined by [3H] clonidine binding being selectively inhibited by an α2-antagonist, yohimbine, but not by an α1-antagonist, prazosin, or a β-antagonist propranolol. Catecholamine responsiveness to adenylate cyclase in hepatocytes also increased during treatment with 3'-MeDAB. However, the efficacy of norepinephrine (NE) in activating cyclase was lower than that of isoproterenol (IPN) during 4 to 8 weeks of the carcinogen diet. The difference between the efficacies of IPN and NE resulted from inhibiting adenylate cyclase through α2-adrenoceptors by NE. Therefore, we noticed that the increasing pattern of the number of β-adrenoceptors did not always parallel IPN-stimulated adenylate cyclase activity and that the increase in the number of α2-adrenoceptors preceded the difference between the efficacies of IPN and NE in activating adenylate cyclase. These findings suggest that the emergence of β- and α2-adrenoceptors occurs before the receptors are able to be coupled with the guanine-nucleotide binding proteins in the adenylate cyclase system in the early stage of hepatocar cinogenesis induced by 3'-MeDAB.
