PHARMACOLOGICAL CHARACTERISTICS AND SPECIES-RELATED VARIATIONS OF BETA(3)-ADRENERGIC RECEPTORS

Beta-adrenergic receptors (beta-AR) belong to the large multigenic fam ily of receptors coupled to GTP-binding proteins. Three subtypes have been identified: beta(1)-, beta(2)- and beta(3)-AR. Much of the work d elineating the precise pharmacological comparison of the three beta-AR s has come from investigations with stably transfected Chinese hamster ovary cells (CHO cells). This review discusses the structure and func tion of beta(3)-AR in various species and presents new findings on a n umber of beta(3)-AR ligands including carazolol, tertatolol and CL 316 ,243 which were found to be selective and potent beta(3)-AR agonists a nd ZD 2079 and salmeterol which appear to display full but non-subtype selective agonistic activity. Species-related variations of the beta( 3)-AR pharmacology have been shown for propranolol and bupranolol. Wit h the ongoing characterization of the beta(3)-AR at the molecular and cellular level, and with the advent of computer-assisted molecular mod elling to aid in the determination of the three-dimensional structure of the receptor, it is thought that novel beta(3)-AR compounds will be come available with improved. Selectivity and potency.