CARAZOLOL - A POTENT, SELECTIVE BETA(3)-ADRENOCEPTOR AGONIST

Carazolol is a beta(1)/beta(2) adrenoceptor antagonist of high potency used in the treatment of hypertension. Its affinity for the beta(3)-a drenoceptor was determined in Chinese hamster ovary cells transfected with the gene of the human or the murine beta(3)-adrenoceptor. Carazol ol is recognized with a nanomolar affinity, which positions it among t he best ligands for beta(3)-adrenoceptors. The adenylyl cyclase stimul ation was measured in transfected cells where carazolol acted as a ful l agonist on both murine and human receptor subtypes. Furthermore, in murine adipocyte-like 3T3-F442A cells, which express beta(3)-adrenocep tor naturally, carazolol induced lipolysis. This compound also appeare d to be a useful tool for molecular characterization of the beta(3)-ad renoceptor: unlike the classical beta(3)-adrenoceptor agonists, carazo lol conferred an appreciable protection of receptor binding sites agai nst inactivation by the reducing agent dithiothreitol. The major iodin ated analog of carazolol retained its binding characteristics for the beta(3)-adrenoceptor and remained an efficient adenylylcyclase stimula tor in cells expressing human beta(3)-adrenoceptor.