Objective: To investigate the contribution of beta 3-adrenoceptor activation to sympathetic stimulation of thermogenesis in humans using a sympathomimetic (ephedrine) in combination with a non-selective beta-adrenoceptor antagonist (nadolol).
Design: Three doses (2.5, 5 and 10 mg) of nadolol were used to estimate what fraction of the thermogenic response to ephedrine (30 mg) remained after inhibition of beta 1- and beta 2-adrenoceptor mediated responses.
Subjects: Nine healthy, young male volunteers at rest after an overnight fast.
Measurements: Energy expenditure, respiratory quotient, heart rate, blood pressure and plasma 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 rate, systolic blood pressure and plasma glucose; the other parameters measured did not change significantly. Nadolol caused significant inhibition of all responses, but 43% of the thermogenic response to ephedrine remained after the 2.5 mg dose of nadolol, whereas the same dose completely inhibited the heart rate and plasma glucose responses.
Conclusion: All three beta-adrenoceptor subtypes (beta 1, beta 2 and beta 3) may be involved in ephedrine-induced thermogenesis, but the resistance to complete inhibition by the non-selective antagonist nadolol indicates that at least 40% of the response is mediated by an atypical receptor, which is presumed to be the beta 3-adrenoceptor.