title: Divergent effects of an alpha2-adrenergic antagonist on lipolysis and thermogenesis: interactions with a beta3-adrenergic agonist in rats.
abstract: This study was undertaken in order to test the hypothesis that selective beta3-AR stimulation and simultaneous blockade of alpha2-AR would result in an increase of lipolysis and thermogenesis in rats. Incubation of isolated white adipocytes with the alpha2-AR antagonist yohimbine produced a concentration-dependent increase in glycerol release (P<0.001) for all assayed concentrations (10-12-10-6 M) and potentiated the lipolytic effect of the beta3-AR agonist Trecadrine. However, in vivo administration of yohimbine produced a marked decrease in body temperature (1.3-1.5 degrees C, P<0.001) and blocked the thermogenic effect of Trecadrine when simultaneously administered. A similar response was observed for whole body oxygen consumption. Furthermore, yohimbine did not modify brown adipose tissue oxygen consumption, but blocked the beta3-AR-mediated increase triggered by Trecadrine. Brown adipose tissue UCP-2 and -3 mRNA expression was not changed by yohimbine. In conclusion, the present work indicates that in vitro alpha2-AR blockade by yohimbine potentiates the beta3-AR-mediated stimulation of lipolysis. On the other hand, in vivo alpha2-AR antagonism blocks the thermogenic effects mediated by beta3-AR stimulation, suggesting a possible interplay between the receptors.
authors.affiliation: Department of Physiology and Nutrition, University of Navarra, 31008 Pamplona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.forename: G
authors.initials: G
authors.lastname: Frühbeck
authors.forename: M
authors.initials: M
authors.lastname: Aguado
authors.forename: F I
authors.initials: FI
authors.lastname: Milagro
authors.forename: J
authors.initials: J
authors.lastname: Margareto
authors.forename: A J
authors.initials: AJ
authors.lastname: Martínez
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D005990:Glycerol / Q000097:blood; D007328:Insulin / Q000097:blood; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D010101:Oxygen Consumption / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000502:physiology; D022722:Thermogenesis / Q000187:drug effects*; D000071256:Uncoupling Protein 1; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001592:Benzyl Alcohols; D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000071256:Uncoupling Protein 1; D015016:Yohimbine; C101319:trecadrine; D005990:Glycerol