Endocrinology, Vol 137, 2638-2641, Copyright © 1996 by Endocrine Society

ARTICLES

Pharmacological characterization of a recently described human beta 3- adrenergic receptor mutant

MR Candelore, L Deng, LM Tota, LJ Kelly, MA Cascieri and CD Strader
Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

The beta 3-adrenergic receptor is the predominant subtype of beta- adrenergic receptor expressed in adipose tissue. Recently, a naturally occurring mutation in the human beta 3-receptor gene has been described which results in substitution of the tryptophan residue at position 64 in the first intracellular loop with an arginine residue. The polymorphism, which is prevalent in the human population, has been associated with increases in some parameters of obesity and Type II diabetes. In order to characterize the pharmacological effects of this amino acid substitution, the W64R mutation was made in the human beta 3 receptor gene and the resulting mutant receptor expressed in CHO cells. Activation by various agonists showed no significant differences (t- test, P > 0.05) between the wild type and mutant receptors. These studies show that, when expressed in a heterologous system, the W64R mutant receptor is pharmacologically and functionally indistinguishable from the wild type beta 3-adrenergic receptor.

This article has been cited by other articles:

				S. L. Kirstein and P. A. Insel Autonomic Nervous System Pharmacogenomics: A Progress Report Pharmacol. Rev., March 1, 2004; 56(1): 31 - 52. [Abstract] [Full Text] [PDF]

				M. R. Candelore, L. Deng, L. Tota, X.-M. Guan, A. Amend, Y. Liu, R. Newbold, M. A. Cascieri, and A. E. Weber Potent and Selective Human beta 3-Adrenergic Receptor Antagonists J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 649 - 655. [Abstract] [Full Text]

				J Gros, C. Gerhardt, and A. Strosberg Expression of human (beta)3-adrenergic receptor induces adipocyte-like features in CHO/K1 fibroblasts J. Cell Sci., January 11, 1999; 112(21): 3791 - 3797. [Abstract] [PDF]

				D. S. Fletcher, M. R. Candelore, D. Grujic, B. B. Lowell, S. Luell, V. S. Susulic, and D. E. Macintyre Beta-3 Adrenergic Receptor Agonists Cause an Increase in Gastrointestinal Transit Time in Wild-type Mice, But Not in Mice Lacking the Beta-3 Adrenergic Receptor J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 720 - 724. [Abstract] [Full Text]

				R. Büettner, A. Schäffler, H. Arndt, G. Rogler, J. Nusser, B. Zietz, I. Enger, S. Hügl, A. Cuk, J. Schölmerich, et al. The Trp64Arg Polymorphism of the {beta} 3-Adrenergic Receptor Gene Is Not Associated with Obesity or Type 2 Diabetes Mellitus in a Large Population-Based Caucasian Cohort J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2892 - 2897. [Abstract] [Full Text]

				L. Sun, S. Ishibashi, J.-i. Osuga, K. Harada, K. Ohashi, T. Gotoda, Y. Fukuo, Y. Yazaki, and N. Yamada Clinical Features Associated With the Homozygous Trp64Arg Mutation of the ß3-Adrenergic Receptor : No Evidence for Its Association With Obesity in Japanese Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 941 - 946. [Abstract] [Full Text] [PDF]

				T. Nagase, A. Aoki, M. Yamamoto, H. Yasuda, S. Kado, M. Nishikawa, N. Kugai, T. Akatsu, and N. Nagata Lack of Association between the Trp64Arg Mutation in the {beta}3-Adrenergic Receptor Gene and Obesity in Japanese Men: A Longitudinal Analysis J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1284 - 1287. [Abstract] [Full Text] [PDF]