Isoproterenol and selective agonists stimulate similar atypical beta-adrenoceptors in rat adipocytes.
We have demonstrated previously that (-)isoproterenol triggers lipolysis in rat epididymal fat cells by stimulating both classical (beta 1, beta 2) and atypical beta-adrenoceptors. The contribution of the classical beta-adrenoceptors can be blocked by addition of 3 nM CGP12177(di-4-3[(1,1-dimethylethyl)amino]-(2-hydroxylpropoxy )1,3-dihydro-2H-benzimidazol-2-one hydrochloride). At higher concentrations, CGP12177 triggers lipolysis also, but by stimulating atypical beta-adrenoceptors only. To find out whether (-)isoproterenol and CGP12177 stimulate similar atypical beta-adrenoceptors, we compared their interaction with recognised beta 3-adrenoceptor antagonists: CGP20712 (1-[2-((3-carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl- 4-trifluoromethyl-2-imidazolyl)phenoxy]-propan-2-ol) (beta 1-selective), ICI118551 [erythro-1-(7-methylindan-4-yloxy)-3- (isopropylamine)-butan-2-ol] (beta 2-selective) and the stereoisomers as well as the racemic mixture of propranolol (non-beta 1/beta 2-subtype selective) and of metoprolol (beta 1-selective). There was a highly significant relationship (r = 0.93) between the potencies of these antagonists for inhibiting the lipolytic response to (-)isoproterenol (in the absence of classical beta-adrenoceptor stimulation) and CGP12177. In both cases, propranolol and metoprolol showed also the same degree of stereoselectivity. These findings suggest that (-)isoproterenol and CGP12177 stimulate the same type and/or form of atypical beta-adrenoceptors in rat epididymal adipocytes.
Van Liefde
I
I
Department of Protein Chemistry, Free University Brussels (V.U.B.), St Genesius-Rode, Belgium.
van Witzenburg
A
A
Vauquelin
G
G
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D007545:Isoproterenol / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D007545:Isoproterenol; C033394:CGP 12177