Evidence for a decrease in the efficiency of beta-receptor coupling to adenylate cyclase in liver membranes from sucrose-fed rats.
Sucrose feeding has been shown previously to alter the plasma concentration of several factors which may regulate beta-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 beta-adrenergic receptor-adenylate cyclase system in rat liver plasma membranes. Beta-Adrenergic responsiveness was monitored by measuring isoproterenol stimulation of adenylate cyclase activity, while beta-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 beta-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 beta-adrenergic receptor to adenylate cyclase coupling efficiency is discussed.
Lynch
C J
CJ
Steer
M L
ML
Connors
M R
MR
Schatz
R A
RA
Deth
R C
RC
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008560:Membrane Fluidity; D008745:Methylation; D010743:Phospholipids / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology*
D010743:Phospholipids; D011943:Receptors, Adrenergic, beta; D013395:Sucrose; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol