Effects of verapamil on gastric acid secretion in vitro and in vivo.
The activity of H,K-ATPase, the gastric acid producing enzyme, was concentration dependently inhibited by verapamil in the mM range. Verapamil concentration dependently inhibited acid formation in gastric glands, measured as [14C]aminopyrine accumulation or oxygen consumption. The IC50 values were in the microM range. No inhibition of acid secretion by verapamil was observed in Heidenhain-pouch dogs and stomach-lumen-perfused rats. However, in pylorus-ligated rats an inhibition was observed, this effect is related to its cardiovascular effectiveness. To understand the action of verapamil, its physicochemical properties were considered. Verapamil is a highly lipophilic base with a pKa of 8.7. It accumulates in membranes and in the acidic spaces of the parietal cell. We suggest that the inhibition of vesicular bound H,K-ATPase is dependent on a non-specific accumulation of verapamil in the membrane (detergent effect) and that inhibition of acid production in vitro is due to an additional accumulation of the drug in acidic compartments, leading to an impaired function of the proton pump. Verapamil does not decrease acid secretion in vivo by this mechanism as the required dose would be higher than the dose that causes a strong depression of the cardiovascular system.
Herling
A W
AW
Department of Pharmacology, Hoechst AG, Frankfurt, F.R.G.
Ljungström
M
M
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
D000632:Aminopyrine; D014700:Verapamil; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase