title: Beta 3-adrenoceptors in dog adipose tissue: studies on their involvement in the lipomobilizing effect of catecholamines.
abstract: The existence of beta 3-adrenoceptors in adipose tissue and their involvement in the control of lipolysis was investigated in dog. Selective beta 3-adrenergic agonists (BRL 37344, SR 58611A and CGP 12177) and catecholamines (isoproterenol and norepinephrine) activated lipolysis in isolated adipocytes (order of potency: isoproterenol > BRL 37344 > norepinephrine > CGP 12177 > SR 58611A). The lipolytic effect of 0.05 microM BRL 37344 was antagonized by the nonselective beta-AR antagonists, but the selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists were ineffective. Infused to conscious dogs, beta 3-adrenergic agonists increased plasma nonesterified fatty acids levels with an order of potency equivalent to that defined in lipolysis. The lipomobilizing effect induced by the administration of an alpha 2-antagonist (0.01 mg/kg RX 821002 i.v.) was suppressed by bupranolol (0.5 mg/kg) or the combination of CGP 20712A and ICI 118551 (0.25 mg/kg each). The effect of 0.05 mg/kg RX 821002 was only partially suppressed by the same beta-antagonist combination, whereas bupranolol totally abolished it. At 0.5 mg/kg, the RX 821002 effect was not modified by beta-antagonists. The lipomobilization due to infusion of catecholamines (0.1, 0.5 or 5 micrograms/kg/min norepinephrine or 5 micrograms/kg/min epinephrine) was always suppressed by bupranolol or the combination of selective beta-antagonists. Thus dog adipocytes express functional beta 3-ARs. Their stimulation induces lipid mobilization. The lipomobilization of exogenously administered catecholamines is due only to the recruitment of beta 1- or beta 2-ARs. However, endogenous catecholamines released after sympathetic nervous system activation could stimulate beta 3-ARs in adipocytes only if a high level of sympathetic nervous system activity is realized.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 317, Faculté de Médecine, Université Paul Sabatier, France.
authors.forename: J
authors.initials: J
authors.lastname: Galitzky
authors.forename: M
authors.initials: M
authors.lastname: Reverte
authors.forename: C
authors.initials: C
authors.lastname: Carpene
authors.forename: M
authors.initials: M
authors.lastname: Lafontan
authors.forename: M
authors.initials: M
authors.lastname: Berlan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002046:Bupranolol / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D002046:Bupranolol; C033394:CGP 12177; D009638:Norepinephrine; D004837:Epinephrine