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 si milar to that of other species: in particular, high efficiency of the two s elective beta(3)-adrenoceptor agonists, CL 316,243 (disodium(R,R)-5[2[[2-(c hlorophenyl)-2hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylat e) and ICI 201651 ((R)-4-(2-hydroxy-3-phenoxypropylaminoethoxy) acetic acid ) and a low affinity for the radioligand (-)-[3-I-125]-iodocyanopindolol. I nterestingly, CGP 12177A ((+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimid azol-2-one), which is described as a partial agonist for the human receptor , was a full agonist for the canine receptor. After expression and stimulat ion of the canine beta(3)-adrenoceptor in stably transfected Chinese hamste r ovary cells there was a very low accumulation of cAMP, suggesting weak co upling to Gs-protein and adenylyl cyclase. However, the response was much b etter in human embryonal kidney cells transfected with the canine beta(3)-a drenoceptor gene. The cloning of the canine beta(3)-adrenoceptor and the in sights gained from its pharmacological characterization may allow the devel opment of selective compounds for use in the treatment of obese dogs. (C) 1 998 Elsevier Science B.V. All rights reserved.