Elevated level of β-adrenergic receptors in hepatocytes from regenerating rat liver: Time study of [ 125I]iodocyanopindolol binding following partial hepatectomy and its relationship to catecholamine-sensitive adenylate cyclase

Abstract

Hepatocytes from regenerating rat liver show an enhanced epinephrine-sensitive adenylate cyclase activity and cAMP response, which may be involved in triggering of the cell proliferation. We have determined adrenergic receptors and adenylate cyclase activity in hepatocytes isolated at various time points after partial hepatectomy. The number of β-adrenergic receptors, measured by binding of [ 125I]iodocyanopindolol ([ 125I]CYP) to a particulate fraction prepared from isolated hepatocytes, increased rapidly after partial hepatectomy as compared with sham-operated or untreated controls. The maximal increase, which was observed at 48 h, was between 5- and 6-fold (from ~1 800 to ~ 10 500 sites per cell). Thereafter, the number of β-adrenergic receptors decreased gradually. Competition experiments indicated β 2-type receptors. Parallelism was found between the change in the number of β 2-adrenergic receptors and the isoproterenol-responsive adenylate cyclase activity. The number of α 1-adrenergic receptors, determined by binding of [ 3H]prazosin, was transiently lowered by about 35% at 18–24 h, with no significant change in K d . Although the results of this study do not exclude the possibility of post-receptor events, they suggest that the increased number of β 2-adrenergic receptors is a major factor responsible for the enhanced catecholamine-responsive adenylate cyclase activity in regenerating liver.