Effect of verapamil on purified bovine carbonic anhydrase. An in vitro study

Relying on previous data which prove the activation of purified and gastric mucosa carbonic anhydrase by interaction of histamine with calcium ions, the present paper investigates the effect of verapamil, a specific antagonist of calcium transport, on purified bovine red cell carbonic anhydrase. In vitro determination of enzymatic activity according to Maren's micromethod showed that verapamil, in concentrations ranging from 10(-8)-10(-3) mol/l inhibits carbonic anhydrase basal activity in a dose-dependent manner. Thus, at 10(-3) mol/l verapamil concentration - representing its maximal effect - carbonic anhydrase basal activity drops from 2114 +/- 244 IU to 1100 +/- 86 IU (p less than 0.01). At this concentration, the drug antagonizes the activating effect of histamine: while maximum concentration (10(-2) mol/l) of histamine activates the enzyme from 2116 +/- 182 IU to 3979 +/- 411 IU the enzyme activity in the presence of verapamil changes in a non-significant way to 2162 +/- 148 IU (p less than 0.10). As calcium was omitted from the in vitro system, the mechanism described here is probably independent of ion transport inhibition. The physiologic importance of this effect for gastric secretion is to be further clarified.