Role of beta1- and beta3-adrenoceptors in the regulation of lipolysis and thermogenesis in rat brown adipocytes.
To evaluate the physiological functions of beta1-, beta2-, and beta3-adrenoceptors (ARs) in brown adipose tissue, the lipolytic and respiratory effects of various adrenergic agonists and antagonists were studied in rat brown adipocytes. The beta-agonists stimulated both lipolysis and respiration (8-10 times above basal levels), with the following order of potency (concentration eliciting 50% of maximum response): CL-316243 (beta3) > BRL-37344 (beta3) > isoproterenol (mainly beta1/beta2) > norepinephrine (NE; mainly beta1/beta2) > epinephrine (mainly beta1/beta2) >> dobutamine (beta1) >> procaterol (beta2). Schild plot coefficients of competitive inhibition experiments using ICI-89406 (beta1 antagonist) revealed that more than one type of receptor mediates NE action. It is concluded from our results that 1) NE, at low plasma levels (1-25 nM), stimulates lipolysis and respiration mainly through beta1-ARs, 2) NE, at higher levels, stimulates lipolysis and respiration via both beta1- and beta3-ARs, 3) beta2-ARs play only a minor role, and 4) beta3-ARs may represent the physiological receptors for the high NE concentrations in the synaptic cleft, where the high-affinity beta1-ARs are presumably desensitized. It is also suggested that lipolysis represents the flux-generating step regulating mitochondrial respiration.
Atgié
C
C
Department of Physiology, Faculty of Medicine, Laval University, Quebec, Canada.
D'Allaire
F
F
Bukowiecki
L J
LJ
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D017265:Procaterol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D022702:Receptors, Adrenergic, beta-3
D000316:Adrenergic alpha-Agonists; D004149:Dioxoles; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D004280:Dobutamine; C057368:BRL 37344; D007545:Isoproterenol; D009638:Norepinephrine; D017265:Procaterol; D004837:Epinephrine