Activation of carbonic anhydrase by beta-adrenergic agonists and inhibition by beta-adrenergic blockers.

Knowing the in vitro and in vivo gastric secretory effects of beta-adrenergic agonists and antagonists, as well as the role of carbonic anhydrase in the gastric HCl production, we investigated the effect of some beta-adrenoceptor agonists (isoprenaline and orciprenaline) and antagonists (propranolol, timolol, atenolol, pindolol, acebutolol, metoprolol, exoxprenolol) on the purified, human red blood cell and gastric mucosa carbonic anhydrase. All the drugs were added to enzymatic preparations in a concentration range of 10(-7)-10(-3) M, the enzymatic activity being determined according to Maren's micro-method. Dose-response relationships were plotted for each drug. The activating effect of the beta-adrenergic agonists isoprenaline and orciprenaline on all the three species of carbonic anhydrase was dose-dependent, maximum effect being reached at 10(-3) M, when a highly significant (p less than 0.001) enzymatic activation was achieved. Beta-adrenergic blocking drugs decreased significantly the activity of carbonic anhydrase, thus, the activity of purified enzyme decreased with propranolol depending on the dose from 2140 +/- 68 to 1060 +/- 82 I.U. (p less than 0.001), that of red blood cell enzyme from 3340 +/- 280 to 1050 +/- 180 I.U. (p less than 0.001) and that of gastric mucosa enzyme from 2.1 +/- 0.2 to 1.1 +/- 0.1 E.U./mg bioptic sample. They also antagonized dose-dependently the activating effect of beta-adrenergic agonists on the enzyme. The results suggest that carbonic anhydrase might be one of the sites of beta-adrenoceptors, further studies using specific radioligands being necessary to elucidate whether these effects represent the interaction of these drugs with their specific receptor or if they are unspecific pharmacologic effects.