DIFFERENTIAL RELEVANCE OF BETA-ADRENOCEPTOR SUBTYPES IN MODULATING THE RAT BROWN ADIPOCYTES FUNCTION

The potencies and intrinsic activities on cyclic AMP accumulation and lipolysis of various selective beta(3)-adrenoceptor agonists were stud ied in brown adipocytes and compared to those of the nonselective, (-) -isoprenaline, and conventional beta(1)-(dobutamine) and beta(2)-adren oceptor (salbutamol) agonists. (-)-Isoprenaline, dobutamine and salbut amol were more potent stimulants of lipolysis than of cyclic AMP accum ulation, while the selective beta(3)-adrenoceptor agonists had similar potencies for these two functions. Apparent pA(2) values of the selec tive beta(1)-(CGP20712A) and beta(2)-adrenoceptor (ICI118551) antagoni sts for inhibition of adenylyl cyclase stimulation by (-)-isoprenaline and the beta(3)-adrenoceptor agonists, BRL37344, SR58611A, and ICI215 001, indicated that (-)-isoprenaline can stimulate the enzyme through a relevant beta(1)-adrenergic component, while the other drugs activat e the enzyme mainly by acting on the beta(3)-adrenoceptors. On the con trary, antagonism of the lipolysis yielded apparent pA(2) values for C GP20712A and ICI118551, suggesting that (-)-isoprenaline, like all the beta(3)-adrenoceptor agonists, stimulated the brown adipose tissue li pid metabolism mainly through an action on beta(3)-adrenoceptors.