Genomic Cloning And Species-Specific Properties Of The Recombinant Canine Beta(3)-Adrenoceptor

A molecular clone encoding beta(2)-adrenoceptor was isolated from a canine genomic library. The cloned receptor exhibited a pharmacological profile similar to that of other species: in particular, high efficiency of the two selective beta(3)-adrenoceptor agonists, CL 316,243 (disodium(R,R)-5[2[[2-(chlorophenyl)-2hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate) and ICI 201651 ((R)-4-(2-hydroxy-3-phenoxypropylaminoethoxy) acetic acid) and a low affinity for the radioligand (-)-[3-I-125]-iodocyanopindolol. Interestingly, CGP 12177A ((+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one), which is described as a partial agonist for the human receptor, was a full agonist for the canine receptor. After expression and stimulation of the canine beta(3)-adrenoceptor in stably transfected Chinese hamster ovary cells there was a very low accumulation of cAMP, suggesting weak coupling to Gs-protein and adenylyl cyclase. However, the response was much better in human embryonal kidney cells transfected with the canine beta(3)-adrenoceptor gene. The cloning of the canine beta(3)-adrenoceptor and the insights gained from its pharmacological characterization may allow the development of selective compounds for use in the treatment of obese dogs. (C) 1998 Elsevier Science B.V. All rights reserved.