MOLECULAR-CLONING AND PHARMACOLOGICAL CHARACTERIZATION OF THE BOVINE BETA-3-ADRENERGIC RECEPTOR

A full-length clone encoding a beta-adrenergic receptor was isolated f rom a bovine brown adipose tissue cDNA library. By comparative sequenc e analysis, and pharmacological characterization of a Chinese hamster ovary cell line expressing the full-length cDNA, it was shown that the product of the cloned gene is the bovine equivalent of the atypical b eta 3-adrenergic receptor previously described in human, mouse, and ra t [Strosberg, A. D. (1993) Prot. Sci. 2, 1198-1209]. The cloned recept or exhibits a pharmacological profile very similar to those from other species. In particular, the receptor has high affinity for BRL 37344 2-(3-chlorophenyl)ethylamino]propyl)phenoxyacetate sodium salt sesquih ydrate], and low affinity for the iodinated ligand(-)-[3-I-125]-iodocy anopindolol. The bovine beta 3-adrenergic receptor has high affinity f or beta 1-adrenergic receptor and beta 2-adrenergic receptor antagonis ts including ICI 201651 henoxypropylaminoethoxy)-N-(2-methoxyethyl)phe noxy acetic acid], carazolol, and CGP 12177A t-butylamino-2-hydroxypro poxy)benzimidazol-2-one]. In contrast to the murine beta 3-adrenergic receptor, both bupranolol and (-)-propranolol were partial agonists of the bovine receptor. The isolation of the bovine beta 3-adrenergic re ceptor, and information obtained from detailed pharmacological profili ng may allow for the development of selective compounds for producing beef cattle with a low-body-mass index, and also aid the ongoing searc h for more selective agonists for the human receptor.