MOLECULAR CHARACTERIZATION OF THE MOUSE BETA-3-ADRENERGIC RECEPTOR - RELATIONSHIP WITH THE ATYPICAL RECEPTOR OF ADIPOCYTES

The gene encoding the murine beta-3-adrenergic receptor (beta-3AR) has been isolated. It translates into a polypeptide of 388 amino acid residues which shows 82% overall homology with the human beta-3AR. In Southern blot experiments, a probe derived from the murine beta-3AR gene hybridizes to a unique restriction fragment in the murine and human genomes. In both species, the beta-3AR gene is located on chromosome 8, in regions (8A2 --> 8A4 in mouse, and 8p11 --> 8p12 in man) which are conserved between mouse and man. The pharmacological profile of the mouse beta-3AR strongly resembles that of the human beta-3AR. It is characterized by a low affinity toward the radiolabelled beta-adrenergic antagonist [I-125]Iodocyano-pindolol and a low efficiency of other antagonists such as propranolol, ICI 118551 or CGP 20712A to inhibit cAMP production induced by isoproterenol. Another salient feature shared by the murine and the human beta-3ARs is the very potent effect of the lipolytic compound BRL 37344 on cAMP accumulation and the partial agonistic effect of the beta-1- and beta-2-adrenergic antagonists CGP 12177A, oxprenolol and pindolol. These properties are verv close to those ascribed to the atypical beta-AR of rodent adipocytes. In addition, Northern blot analyses indicate that the beta-3AR gene is mainly expressed in mouse brown and white adipose tissues, suggesting that the murine beta-3AR described here is the atypical beta-AR involved in the control of energy expenditure in fat tissue.