CONTRIBUTION OF BETA(3)-ADRENOCEPTOR ACTIVATION TO EPHEDRINE INDUCED THERMOGENESIS IN HUMANS

OBJECTIVE: To investigate the contribution of beta(3)-adrenoceptor act ivation to sympathetic stimulation of thermogenesis in humans using a sympathomimetic (ephedrine) in combination with a non-selective beta-a drenoceptor antagonist (nadolol). DESIGN: Three doses (2.5, 5 and 10 m g) of nadolol were used to estimate what fraction of the thermogenic r esponse to ephedrine (30 mg) remained after inhibition of beta(1)- and beta(2)-adrenoceptor mediated responses. SUBJECTS: Nine healthy, youn g male volunteers at rest after an overnight fast.MEASUREMENTS: Energy expenditure, respiratory quotient, heart rate, blood pressure and pla sma potassium, glucose, lactate, glycerol, NEFA and triglycerides were measured before, and for 3 h after treatment with placebo, ephedrine and ephedrine plus three doses of nadolol. RESULTS: Ephedrine produced significant increases in energy expenditure (thermogenesis), heart ra te, systolic blood pressure and plasma glucose; the other parameters m easured did not change significantly. Nadolol caused significant inhib ition of all responses, but 43% of the thermogenic response to ephedri ne remained after the 2.5 mg dose of nadolol, whereas the same dose co mpletely inhibited the heart rate and plasma glucose responses. CONCLU SION: All three beta-adrenoceptor subtypes (beta(1), beta(2) and beta( 3)) may be involved in ephedrine-induced thermogenesis, but the resist ance to complete inhibition by the non-selective antagonist nadolol in dicates that at least 40% of the response is mediated by an atypical r eceptor, which is presumed to be the beta(3)-adrenoceptor.