title: Selective up-regulation of alpha1a-adrenergic receptor protein and mRNA in brown adipose tissue by neural and beta3-adrenergic stimulation.
abstract: Previous studies have shown that neural stimulation of brown adipose tissue (BAT) reorganizes the expression and activity of signaling proteins in the beta-adrenergic adenylyl cyclase pathway. Cold stress increases neural stimulation of BAT and increases alpha1-adrenergic receptor number; however, the alpha1 receptor subtype involved and the mechanism of up-regulation by cold stress have not been determined. Using reverse transcription/polymerase chain reaction analysis and nuclease protection assay, BAT was demonstrated to express mRNAs encoding alpha1a and alpha1d, but not alpha1b, receptors. Parallel pharmacologic studies of BAT membranes and recombinant alpha1a and alpha1d receptors expressed in COS-7 cells demonstrated that alpha1a receptors predominate in BAT. Exposure of rats to 4 degrees for 4 days increased alpha1a receptors and mRNA in BAT but did not alter expression of alpha1d receptors or mRNA. The induction of alpha1a receptor and mRNA level by cold stress was prevented by selective surgical denervation of BAT. Furthermore, alpha1a receptor and mRNA expression could be induced in warm-adapted rats by infusions of the selective beta3-adrenergic receptor agonist CL 316,243. These data indicate that neural activation of beta3-adrenergic receptors is an important determinant of alpha1a adrenergic receptor expression in BAT.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Granneman
authors.forename: Y
authors.initials: Y
authors.lastname: Zhai
authors.forename: K N
authors.initials: KN
authors.lastname: Lahners
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000294:innervation* / Q000648:ultrastructure*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D004558:Electric Stimulation; D007457:Iodine Radioisotopes; D008297:Male; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D013564:Sympathetic Nervous System / Q000502:physiology; D044024:Tetralones; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D018076:DNA, Complementary; D004149:Dioxoles; D007457:Iodine Radioisotopes; D010627:Phenethylamines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D044024:Tetralones; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C048008:2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone