Atypical beta-adrenergic receptor in 3T3-F442A adipocytes. Pharmacological and molecular relationship with the human beta 3-adrenergic receptor.

摘要: Expression of ligand binding properties for an atypical beta-adrenergic receptor (beta-AR) subtype was studied during the adipose differentiation murine 3T3-F442A cells and compared with that human beta 3-AR expressed in Chinese hamster ovary stably transfected gene (CHO-beta 3 cells) Emorine, L. J., Marullo, S., Briend-Sutren, M. M., Patey, G., Tate, K., Delavier-Klutchko, C., Strosberg, A. D. (1989) Science 245, 1118-1121). adipocytes exhibited high low affinity sites (-)-4-(3-t-butylamino-2-hydroxypropoxy) [5,7-3H]benzimidazole-2-one ((-)-[3H]CGP-12177) (KD = 1.2 38.3 nM) (-)-[125I]iodocyanopindolol ([125I]CYP) 47 1,510 pM). The corresponded to classical 1- 2-AR subtypes whereas KD values radioligands were similar those measured CHO-beta 28 nM 1,890 pM (-)-[3H]CGP12177 [125I]CYP, respectively). These undetectable preadipocytes but represented about 90% total beta-ARs adipocytes. beta-AR add similarly affinities (Ki 3-5 microM) (+/-)-(2-(3-carbamoyl-4-hydroxyphenoxy)ethylamino-3)-(4-(1-methyl- 4- trifluormethyl-2-imidazolyl)-phenoxy)-2-propanol methane sulfonate (CGP20712A) or erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylaminob utan-2-ol (ICI118551), highly selective antagonists, respectively, agreement poor inhibitory effect compounds on (-)-isoproterenol (IPR)-stimulated adenylate cyclase activity. Atypical had 10-50 times higher sodium-4-(2-[2-hydroxy-2-(3-chlorophenyl)ethylamino]propyl)phenoxyace tate sesquihydrate (BRL37344) than 1-AR subtype. This correlates potent lipolytic BRL37344 rank order potency agonists functional studies greater IPR less (-)-norepinephrine (-)-epinephrine both 3T3 cells. As cells, 2-antagonists CGP12177, oxprenolol, pindolol partial Although preadipocytes, a major mRNA species 2.3 kilobases (kb) minor one 2.8 kb observed by hybridization specific probe.(ABSTRACT TRUNCATED AT 400 WORDS)