PT - JOURNAL ARTICLE AU - M L Cohen AU - J G Granneman AU - A Chaudhry AU - K W Schenck AU - D J Cushing AU - A D Palkowitz TI - Is the "atypical" beta-receptor in the rat stomach fundus the rat beta 3 receptor? DP - 1995 Jan 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 446--451 VI - 272 IP - 1 4099 - http://jpet.aspetjournals.org/content/272/1/446.short 4100 - http://jpet.aspetjournals.org/content/272/1/446.full SO - J Pharmacol Exp Ther1995 Jan 01; 272 AB - The rat gastric fundus is known to possess an "atypical" beta-adrenergic receptor that mediates relaxation to isoproterenol. The purpose of this study was to characterize the relationship between this "atypical" beta receptor in the rat stomach and the cloned rat beta 3 receptor by taking advantage of highly selective pharmacological and molecular biological probes of the beta 3 receptor. Nuclease protection analysis of RNA from the rat gastric fundus identified beta 3 receptor mRNA whose levels in the stomach were exceeded only by those in adipose tissue. Pharmacological analysis of the recombinant rat beta 3 receptor expressed in Chinese hamster ovary cells indicated low affinity of propranolol with a Ki value of 2.3 microM. Therefore, 0.3 microM propranolol was chosen as a concentration that would completely block beta 1 and beta 2 receptors (Ki = 1-5 nM) but would leave beta 3 receptors largely intact in the rat stomach fundus. In the presence of propranolol, several beta-adrenergic receptor agonists relaxed the rat stomach fundus with a rank potency order of (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3- benzodioxole-2,2-dicarboxylate (CL316,243) > isoproterenol > norepinephrine = epinephrine = dl-4-3[(1,1-dimethylethyl)amino]-2- hydroxylproproy]1,3 dihydro-2H-benzimidazol-2-one hydrochloride (CGP12177) > clenbuterol > terbutaline > pindolol. Isoproterenol, norepinephrine and epinephrine were full agonists, whereas (R,R)-5-[2-[[2-(3-chlorophenyl)-2- hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-dicarboxylate was only a partial agonist with 66% intrinsic activity relative to isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)