An in vitro study of enhanced H+ diffusion by urease action on urea. Implications for Helicobacter pylori-associated peptic ulceration.

The in vitro effect of urea and hydrolysis of urea by urease on mucus H+ permeability is reported here. The effective DHCl values indicate a strong pH dependence for H+ diffusion in both water and mucus layers, with no apparent trend at concentrations between 1 and 50 mM urea. However, the estimated DHCl at near-neutral and alkaline pH are 4- to 10-fold lower through mucus than through aqueous films. Moreover, the pKa values of HCO3- and NH3 (generated by urease action on urea) had a profound effect on measured DHCl. These in vitro studies suggest that a high local concentration of NH3 and HCO3- within the mucus layer, generated by the action of Helicobacter pylori urease on endogenous intragastric urea, could greatly accelerate proton flux to the surface epithelium by operation of a buffer shuttle. This results in enhanced H+ permeability, particularly at pKa values of HCO3- and NH3, and in extreme circumstances it may result in gastric ulcer formation.