Do beta 3-adrenoceptors mediate metabolic responses to isoprenaline

Q J Med. 1993 Sep;86(9):595-600.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Atenolol / metabolism
  • Basal Metabolism
  • Fatty Acids, Nonesterified / metabolism
  • Female
  • Glucose / metabolism
  • Glycerol / metabolism
  • Humans
  • Insulin / metabolism
  • Isoproterenol / metabolism*
  • Lactates / metabolism
  • Lactic Acid
  • Male
  • Nadolol / metabolism
  • Receptors, Adrenergic, beta / metabolism*
  • Respiration


  • Fatty Acids, Nonesterified
  • Insulin
  • Lactates
  • Receptors, Adrenergic, beta
  • Lactic Acid
  • Nadolol
  • Atenolol
  • Glucose
  • Isoproterenol
  • Glycerol