Divergent effects of an alpha(2)-adrenergic antagonist on lipolysis and thermogenesis: Interactions with a beta(3)-adrenergic agonist in rats

This study was undertaken in order to test the hypothesis that selective be ta (3)-AR stimulation and simultaneous blockade of alpha (2)-AR would resul t in an increase of lipolysis and thermogenesis in rats. Incubation of isol ated white adipocytes with the alpha (2)-AR antagonist yohimbine produced a concentration-dependent increase in glycerol release (P <0.001) for all as sayed concentrations (10(-12)-10(-6) M) and potentiated the lipolytic effec t of the beta (3)-AR agonist Trecadrine. However, in vivo administration of yohimbine produced a marked decrease in body temperature (1.3-1.5 degreesC , P <0.001) and blocked the thermogenic effect of Trecadrine when simultane ously administered. A similar response was observed for whole body oxygen c onsumption. Furthermore, yohimbine did not modify brown adipose tissue oxyg en consumption, but blocked the beta (3)-AR-mediated increase triggered by Trecadrine. Brown adipose tissue UCP-2 and -3 mRNA expression was not chang ed by yohimbine. In conclusion, the present work indicates that in vitro al pha (2)-AR blockade by yohimbine potentiates the beta (3)-AR-mediated stimu lation of lipolysis. On the other hand, in vivo alpha (2)-AR antagonism blo cks the thermogenic effects mediated by beta (3)-AR stimulation, suggesting a possible interplay between the receptors.