title: Beta 3-adrenergic activation of adenylyl cyclase in mouse white adipocytes: modulation by GTP and effect of obesity.
abstract: Lipolysis and adenylyl cyclase (AC) activation in response to beta-adrenergic agents are abnormally low in white epididymal adipose tissue (WAT) of the ob/ob mouse. The abundance of G-proteins (Gs alpha and Gi alpha) linked to AC is also abnormally low. By contrast, beta-adrenergic receptor (beta-AR) levels were previously found to be normal in WAT and elevated in liver. The relative importance of various forms of the beta-AR in mouse WAT was reassessed in view of the discovery of the beta 3-AR. The results show that (1) the beta 3-AR is mainly responsible for AC activation in lean-mouse WAT; (2) the beta 3-AR is only partly responsible for AC activation in obese mouse WAT; and (3) GTP modulates beta 3--but not beta 1--or beta 2-AR activation of AC in a biphasic manner. Therefore, the beta 3-AR appears responsible for the well-known bimodal effect of GTP on beta-adrenergic receptor-mediated AC activity in WAT.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Ottawa, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Bégin-Heick
mesh_terms: D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D017667:Adipocytes / Q000201:enzymology*; D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D015342:DNA Probes; D018076:DNA, Complementary; D004149:Dioxoles / Q000494:pharmacology; D004789:Enzyme Activation; D004822:Epididymis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000201:enzymology*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D013851:Thinness / Q000201:enzymology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000318:Adrenergic beta-Agonists; D015342:DNA Probes; D018076:DNA, Complementary; D004149:Dioxoles; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D010566:Virulence Factors, Bordetella; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D006160:Guanosine Triphosphate; D011433:Propranolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D000420:Albuterol