Molecular cloning and pharmacological characterization of the bovine beta 3-adrenergic receptor.
A full-length clone encoding a beta-adrenergic receptor was isolated from a bovine brown adipose tissue cDNA library. By comparative sequence 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 beta 3-adrenergic receptor previously described in human, mouse, and rat [Strosberg, A. D. (1993) Prot. Sci. 2, 1198-1209]. The cloned receptor exhibits a pharmacological profile very similar to those from other species. In particular, the receptor has high affinity for BRL 37344 [(RR,SS)-(+/-)-4-(2'-[2-hydroxy-2-(3- chlorophenyl)ethylamino]propyl)phenoxyacetate sodium salt sesquihydrate], and low affinity for the iodinated ligand(-)-[3-125I]-iodocyanopindolol. The bovine beta 3-adrenergic receptor has high affinity for beta 1-adrenergic receptor and beta 2-adrenergic receptor antagonists including ICI 201651 [(R)-4-(2-hydroxy-3-phenoxypropylaminoethoxy)-N-(2- methoxyethyl)phenoxy acetic acid], carazolol, and CGP 12177A [(+/-)-4-(3-t-butylamino-2- hydroxypropoxy)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 receptor, and information obtained from detailed pharmacological profiling may allow for the development of selective compounds for producing beef cattle with a low-body-mass index, and also aid the ongoing search for more selective agonists for the human receptor.
Piétri-Rouxel
F
F
Institut Cochin de Génétique Moléculaire, Centre Nationale de la Recherche Scientifique, UPR, Paris, France.
Lenzen
G
G
Kapoor
A
A
Drumare
M F
MF
Archimbault
P
P
Strosberg
A D
AD
Manning
B S
BS
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002417:Cattle; D003001:Cloning, Molecular; D006224:Cricetinae; D008969:Molecular Sequence Data; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3; D011994:Recombinant Proteins / Q000096:biosynthesis
D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D011994:Recombinant Proteins