Cholesterol modulation of beta-adrenergic receptor characteristics.
Cholesterol, a major structural component of plasma membranes, has a profound influence on cell surface receptor characteristics and on adenylate cyclase activity. beta-Adrenergic receptor number, adenylate cyclase activity, and receptor-cyclase coupling were assessed in rat lung membranes following preincubation with cholesteryl hemisuccinate. beta-Adrenergic receptor number increased by 50% without a change in antagonist affinity. However, beta-adrenergic receptor affinity for isoproterenol increased 2-fold as a result of an increase in the affinity of the isoproterenol high-affinity binding site. The increase in agonist affinity did not potentiate hormone-stimulated adenylate cyclase activity, which decreased 3-fold following cholesterol incorporation. However, the ratio of isoproterenol to GTP-stimulated activity was unchanged with cholesterol. Stimulation distal to the receptor by GTP, NaF, GppNHp, Mn2+ and forskolin also demonstrated 50-80% reduced enzyme activity following cholesterol incorporation. These data suggest that membrane cholesterol incorporation decreases catalytic unit activity without affecting transduction of the hormone signal.
Scarpace
P J
PJ
O'Connor
S W
SW
Abrass
I B
IB
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D002788:Cholesterol Esters; D011943:Receptors, Adrenergic, beta; D002784:Cholesterol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C013440:cholesteryl succinate