Do β3-adrenoceptors mediate metabolic responses to isoprenaline
We investigated whether the putative β3-adrenoceptors mediated metabolic responses to isoprenaline. Seven normal volunteers received infusions of isoprenaline, a (β1, β2 and β3-agonist), at 0.5–3.0 μg/min. They were pretreated with either placebo, 25 mg atenolol (a selective β1 antagonist), or 5, 20 and 80 mg nadolol (which blocks β1 and β2 but not β3-adrenoceptors). Isoprenaline markedly (30.6%) increased basal metabolic rate (BMR): this increase was significantly reduced by 25 mg atenolol but not by 5 mg nadolol. Significant β2-blockade (from tremor data) occurred with 5 mg nadolol but not with 25 mg atenolol. This suggests that β1 but not β2-adrenoceptors are involved in the mediating thermogenic effects of isoprenaline. However, the rise in BMR was not totally blocked even by 80 mg nadolol (9.5%), which produced complete β1/β2 blockade, as evidenced by the elimination of the chronotropic effect of isoprenaline. This implies that the thermogenic response has a non-β1/β2-mediated component. There were also significant increases in plasma free fatty acids, glycerol, glucose, insulin and lactate, but these were completely abolished by β1/2 blockade. Overall, isoprenaline produced an increase in BMR which is only partly due to stimulation of β1-adrenoceptors, and which is not associated with β1/β2-mediated effects on carbohydrate and fat metabolism. This suggests the possibility of thermogenic β3-adrenoceptors in man, although their location and role remain unknown.