Effects of β3-adrenoceptor agonist BRL 37344 on lipomobilization and plasma glucose levels in conscious fasted rabbits

Abstract

The existence of a functional beta 3-adrenoceptor in conscious 24 h fasted rabbits was investigated by studying the effect of BRL 37344 (a beta 3-adrenoceptor agonist) in comparison with CGP 12177 (a beta 1- and beta 2-adrenoceptor antagonist, which also acts as a partial beta 3 agonist) and isoproterenol (a nonselective beta 1-, beta 2-, and beta 3-adrenoceptor agonist) on plasma nonesterified fatty acids (NEFA) and its possible relation with glucose metabolism. All drugs were intravenously infused at the same dose, 0.3 microgram.kg-1.min-1 (30 min), BRL 37344, CGP 12177, and isoproterenol significantly elevated plasma NEFA levels without increasing plasma glucose levels. Isoproterenol elevated plasma insulin and lactate levels, but BRL 37344 and CGP 12177 did not. Bupranolol (0.1 mg/kg, subcutaneously) blocked the BRL 37344 mediated effect on plasma NEFA levels. In the presence of CGP 20712A (1 mg/kg, subcutaneously), ICI 118551 (30 micrograms/kg, subcutaneously), or the mixture of both selective beta-antagonists, BRL 37344 also evoked an increase in plasma NEFA levels, but the response was less pronounced when compared with BRL 37344 alone. These data suggest that in conscious rabbits deprived of food for 24 h (i) BRL 37344 induces lipomobilization through beta 3-adrenoceptor stimuli, but the effect is less than by beta 1- and beta 2-adrenoceptor stimuli, and (ii) an excess of plasma NEFA evoked by BRL 37344 may not necessarily contribute to plasma glucose increases.