Potentiation of beta-adrenoceptor agonist mediated-lipolysis by cholesterol-derived oxysterols.
Cholesterol-derived oxysterols such as cholestanol, cholestanone and coprostanone were able to potentiate epinephrine-induced lipolysis in intact rat adipocytes but not cholesterol. The relative potency of the oxysterols followed the sequence: cholestanone > or = coprostanone > cholestanol. Cholestanone was selected to study its mode of action on epinephrine-induced lipolysis. A sustained increase in the level of cAMP was observed in adipocytes incubated with both cholestanone and epinephrine compared to a transient peaking of cAMP in adipocytes incubated with epinephrine alone. Binding assays using [125I]cyanopindolol (beta-adrenergic receptor antagonist) showed that cholestanone could increase the binding affinity of [125I]-cyanopindolol to beta-adrenergic receptors on rat adipocyte ghost membranes without affecting the total number of binding sites. The results suggest that cholestanone exerts its potentiation effect by facilitating the binding of beta-adrenergic agonist to its receptor.
D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002776:Cholestanes / Q000494:pharmacology*; D004083:Cholestanol / Q000494:pharmacology*; D002778:Cholestanones / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D015394:Molecular Structure; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
D002776:Cholestanes; D002778:Cholestanones; D004083:Cholestanol; D000242:Cyclic AMP; C007123:coprostanone; D004837:Epinephrine