Do beta 3-adrenoceptors mediate metabolic responses to isoprenaline.
We investigated whether the putative beta 3-adrenoceptors mediated metabolic responses to isoprenaline. Seven normal volunteers received infusions of isoprenaline, a (beta 1, beta 2 and beta 3-agonist), at 0.5-3.0 micrograms/min. They were pretreated with either placebo, 25 mg atenolol (a selective beta 1 antagonist), or 5, 20 and 80 mg nadolol (which blocks beta 1 and beta 2 but not beta 3-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 beta 2-blockade (from tremor data) occurred with 5 mg nadolol but not with 25 mg atenolol. This suggests that beta 1 but not beta 2-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 beta 1/beta 2 blockade, as evidenced by the elimination of the chronotropic effect of isoprenaline. This implies that the thermogenic response has a non-beta 1/beta 2-mediated component. There were also significant increases in plasma free fatty acids, glycerol, glucose, insulin and lactate, but these were completely abolished by beta 1/beta 2 blockade. Overall, isoprenaline produced an increase in BMR which is only partly due to stimulation of beta 1-adrenoceptors, and which is not associated with beta 1/beta 2-mediated effects on carbohydrate and fat metabolism. This suggests the possibility of thermogenic beta 3-adrenoceptors in man, although their location and role remain unknown.
Wheeldon
N M
NM
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee.
McDevitt
D G
DG
Lipworth
B J
BJ
D000328:Adult; D001262:Atenolol / Q000378:metabolism; D001481:Basal Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007545:Isoproterenol / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009248:Nadolol / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012119:Respiration
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D011943:Receptors, Adrenergic, beta; D019344:Lactic Acid; D009248:Nadolol; D001262:Atenolol; D005947:Glucose; D007545:Isoproterenol; D005990:Glycerol