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Comparative Study
, 137 (6), 2638-41

Pharmacological Characterization of a Recently Described Human Beta 3-adrenergic Receptor Mutant

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Comparative Study

Pharmacological Characterization of a Recently Described Human Beta 3-adrenergic Receptor Mutant

M R Candelore et al. Endocrinology.

Abstract

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.

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