Evidence for a decrease in the efficiency of β-receptor coupling to adenylate cyclase in liver membranes from sucrose-fed rats

Abstract

Sucrose feeding has been shown previously to alter the plasma concentration of several factors which may regulate β-adrenergic receptors, including corticosteroids and insulin as well as altered sympathetic nervous system (SNS) tone. For this reason we initiated a study of the effects of sucrose feeding on the β-adrenergic receptor-adenylate cyclase system in rat liver plasma membranes, β-Adrenergic responsiveness was monitored by measuring isoproterenol stimulation of adenylate cyclase activity, while β-adrenergic receptor characteristics were evaluated by analyzing [ 125I]iodocyanopindolol ([ 125I]CYP) binding. Rats fed rat chow ad lib. supplemented by drinking water containing 10% sucrose solution exhibited a 50–75% reduction in hepatic isoproterenol-sensitive adenylate cyclase activity. This effect of sucrose was also observed in adrenalectomized (ADX) and 6-hydroxydopamine-pretreated animals, ruling out a causal role for corticosteroids or the sympathetic nervous system respectively. No effect was observed on basal, glucagon-, fluoride- or GTP-stimulated adenylate cyclase. A small but significant decrease in [ 125I]CYP specific binding capacity was observed in liver membranes prepared from sucrose-fed ADX rats, whereas no change in [ 125I]CYP binding capacity was observed in in sucrose-fed normal rats. These observations suggest that β-receptor to adenylate cyclase coupling efficiency is decreased by the sucrose diet. The activities of two membrane-associated phospholipid methyltransferases and the content of endogenous S-adenosylmethionine in liver were reduced by sucrose feeding, implying a defect in the methylation pathway for phosphatidylcholine synthesis. The possible relationship between this latter finding and the observed decrease in β-adrenergic receptor to adenylate cyclase coupling efficiency is discussed.