PHARMACOLOGICAL CHARACTERIZATION OF A RECENTLY DESCRIBED HUMAN BETA-3-ADRENERGIC RECEPTOR MUTANT

The beta 3-adrenergic receptor is the predominant subtype of beta-adre nergic receptor expressed in adipose tissue. Recently, a naturally occ urring mutation in the human beta 3-receptor gene has been described w hich results in substitution of the tryptophan residue at position 64 in the first intracellular loop with an arginine residue. The polymorp hism, 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 s ubstitution, the W64R mutation was made in the human beta 3 receptor g ene and the resulting mutant receptor expressed in CHO cells. Activati on by various agonists showed no significant differences (t-test, P>0. 05) between the wild type and mutant receptors. These studies show tha t when expressed in a heterologous system, the W64R mutant receptor is pharmacologically and functionally indistinguishable from the wild ty pe beta 3-adrenergic receptor.