Pharmacological characteristics and species-related variations of beta 3-adrenergic receptors.
Beta-adrenergic receptors (beta-AR) belong to the large multigenic family of receptors coupled to GTP-binding proteins. Three subtypes have been identified: beta 1-, beta 2- and beta 3-AR. Much of the work delineating the precise pharmacological comparison of the three beta-ARs has come from investigations with stably transfected Chinese hamster ovary cells (CHO cells). This review discusses the structure and function of beta 3-AR in various species and presents new findings on a number of beta 3-AR ligands including carazolol, tertatolol and CL 316,243 which were found to be selective and potent beta 3-AR agonists and 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. With the ongoing characterization of the beta 3-AR at the molecular and cellular level, and with the advent of computer-assisted molecular modelling to aid in the determination of the three-dimensional structure of the receptor, it is thought that novel beta 3-AR compounds will become available with improved selectivity and potency.
Pietri-Rouxel
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Institut Cochin de Génétique Moléculaire, Molecular Immuno-Pharmacology Laboratory, CNRS-UPR 0415, Paris, France.
Strosberg
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AD
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3; D013045:Species Specificity
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3