Effects of fasting on hepatic catecholamine receptors

Abstract

Catecholamines through both aand fl-adrenergic receptors activate glycogenolysis and gluconeogenesis in the rat liver [1-4]. There is considerable evidence that epinephrine activates glycogenolysis through interaction with the al-adrenoceptors in livers of adult rats. Glycogenolytic activation via the fl-receptor is negligible in these animals. The characteristics of catecholamine activation of these processes have been reported to be altered in adrenalectomized [5,6] and hypothyroid rats [7-9]. In these animals, a decrease in a-adrenergic action concomitant with an increase in fl-adrenergic action was observed [5,6,8,9]. It was further reported that the number of a-adrenergic receptors either remained unaltered [5,6], or decreased [9] whereas fl-adrenergic receptor number was shown to increase [6-8]. The increase in fl-receptor numbers was also associated with increases in the catecholamine-sensitive adenylate cyclase activity [5,7,8]. Adrenalectomy as well as abnormal thyroid states often affect animals' food intake and normal weight-gain. We have reported that decreases in hepatic glycogen phosphorylase activities (a form and total) as well as cAMP-dependent protein kinase elution pattern in adrenalectomized rats which lost weight after surgery, resembled those in briefly-fasted rats [5]. These observations prompted us to investigate the effects of fasting on the catecholamine-mediated regulation of hepatic glucose production. Here, we report that 20-24 h fasting resulted in no significant change in the number of binding sites for the mixed al-,a2-adrenergic antagonist [3H]dihydroergocryptine ([3H]DHE). However, there was a 25% decrease in the density of al-adrenergic binding sites labeled with [3H]prazosin, and a 50% reduction in the number of binding sites for the selective a 2-adrenergic antagonist [3H]yohimbine. Reciprocally, there was a marked increase (100%) in the density of the binding sites for the fl-antagonist [125I]iodocyanopindolol ([125I]CYP). In isolated hepatocytes, 20-24 h fasting caused an increase in the catecholamine-sensitive accumulation of cyclic AMP (cAMP) and in gluconeogenesis.