ADRENERGIC-RECEPTORS AND FAT-CELLS - DIFFERENTIAL RECRUITMENT BY PHYSIOLOGICAL AMINES AND HOMOLOGOUS REGULATION

The control of fat cell lipolysis by the catecholamines involves at le ast four different adrenoceptor subtypes; three beta (beta 1-, beta 2- , and beta 3-ARs) and one alpha 2-adrenoceptor(alpha 2-AR). The physio logical importance of the beta- and alpha 2A-ARs varies according to t he species, the sex, the age, the anatomical location of fat deposits and the degree of obesity in humans and animals. The physiological ami nes operate through differential recruitment of these sites on the bas is of their relative affinities. This point has been assessed by in vi tro studies and has partly been confirmed in in vivo experiments using selected alpha/beta-AR antagonists and in situ micro dialysis. The af finity of the beta 3-AR for catecholamines is less than that of the cl assical beta 1- and beta 2-ARs in the various species investigated, Co nversely, it is the alpha 2-AR which exhibit the highest affinity for the physiological amines in all fat cells. The relative order of affin ity of the various fat cell ARs for the physiological amines defined i n binding studies and in vitro assays is alpha 2 > beta 1 greater than or equal to beta 2 > beta 3 for norepinephrine and alpha 2 > beta 2 > beta 1 > beta 3 for epinephrine. When considering differential P-AR r ecruitment by catecholamines, it is the beta-AR which is always activa ted at the lowest norepinephrine levels, whatever the species,while th e activation of the beta 3-AR requires higher norepinephrine levels. I n addition to the differential recruitment, differential regulation by hormones could also occur for each fat cell AR subtype. The alpha 2-a nd beta 3-ARs are less prone to desensitization and down-regulation by comparison with the beta 1- and beta 2-AR.