title: Norepinephrine infusions increase adenylate cyclase responsiveness in brown adipose tissue.
abstract: Previous work from our laboratory demonstrated that exposing rats to cold increases interscapular brown adipose tissue (IBAT) adenylate cyclase activity through a postreceptor modification of the adenylate cyclase system. The cold-induced sensitization is correlated with an increase in the activity of the sympathetic innervation of IBAT, and is prevented by prior surgical denervation of this tissue. The present experiments were aimed at identifying the neurogenic signal that mediates cold-induced sensitization. We found that, like cold exposure, infusions of norepinephrine increased adenylate cyclase activity and enhanced the ability of cholera toxin to ADP-ribosylate the stimulatory regulatory protein of adenylate cyclase (Gs) in warm-adapted rats whose IBAT had been denervated surgically. Infusions of isoproterenol increased adenylate cyclase responsiveness more potently than norepinephrine; however, the maximal effect achieved by isoproterenol was less than that produced by norepinephrine. Infusions of phenylephrine and clonidine had no effect on adenylate cyclase responsiveness. The effects of low doses of isoproterenol, however, were greatly potentiated by coinfusion of phenylephrine. Furthermore, the sensitizing effects of norepinephrine could be blocked by either propranolol or prazosin, indicating that the effects of norepinephrine require simultaneous stimulation of beta and alpha-1 adrenergic receptors.
authors.affiliation: Center for Cell Biology, Sinai Research Institute, Detroit, Michigan.
authors.forename: J G
authors.initials: JG
authors.lastname: Granneman
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000032:analysis*; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D003080:Cold Temperature; D019204:GTP-Binding Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013997:Time Factors
chemical_list: D011942:Receptors, Adrenergic, alpha; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine