Differential relevance of beta-adrenoceptor subtypes in modulating the rat brown adipocytes function.
The potencies and intrinsic activities on cyclic AMP accumulation and lipolysis of various selective beta 3-adrenoceptor agonists were studied in brown adipocytes and compared to those of the nonselective, (-)-isoprenaline, and conventional beta 1- (dobutamine) and beta 2-adrenoceptor (salbutamol) agonists. (-)-Isoprenaline, dobutamine and salbutamol were more potent stimulants of lipolysis than of cyclic AMP accumulation, while the selective beta 3-adrenoceptor agonists had similar potencies for these two functions. Apparent pA2 values of the selective beta 1-(CGP20712A) and beta 2-adrenoceptor (ICI118551) antagonist for inhibition of adenylyl cyclase stimulation by (-)-isoprenaline and the beta 3-adrenoceptor agonists, BRL37344, SR58611A, and ICI215001, indicated that (-)-isoprenaline can stimulate the enzyme through a relevant beta 1-adrenergic component, while the other drugs activate the enzyme mainly by acting on the beta 3-adrenoceptors. On the contrary, antagonism of the lipolysis yielded apparent pA2 values for CGP20712A and ICI118551, suggesting that (-)-isoprenaline, like all the beta 3-adrenoceptor agonists, stimulated the brown adipose tissue lipid metabolism mainly through an action on beta 3-adrenoceptors.
Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, University of Milan, Italy.
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Carruba
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D005990:Glycerol / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D005990:Glycerol