Regulation of heat production of brown adipocytes via typical and atypical beta-adrenoceptors in the rat

Abstract

Previous studies in our laboratory demonstrated that microcalorimetry is an appropriate method for estimating the physiological function of isolated rat brown adipocytes. In the present study, to elucidate the mode of action of typical and atypical beta-adrenoceptors on heat production of this cell, the effect of novel adrenergic beta 3-agonists was compared with that of other typical adrenergic reagents by direct microcalorimetry. Isoproterenol and beta 3-agonists, BRL37344, ICI215001, and CGP12177, increased heat production in a dose-dependent manner, however, phenylephrine had no effect. Propranolol and pindolol did not increase the heat production but attenuated the effect of isoproterenol and BRL37344 in a dose-dependent manner. Molar IC50 values of propranolol and pindolol for BRL37344 were about 10(-5) and 3 x 10(-6) M, respectively, whereas those of the two antagonists for isoproterenol were about 3 x 10(-7)M. The pA2 values by Schild analysis of propranolol vs. isoproterenol and BRL37344 were 7.91 and 6.13, respectively. These results suggest that heat production may be regulated via both beta 3- and typical beta-adrenoceptors in brown adipocytes.