An in Vitro Study of Enhanced H⁺ Diffusion by Urease Action on Urea: Implications for Helicobacter pylori-Associated Peptic Ulceration

Abstract

The in vitro effect of urea and hydrolysis of urea by urease on mucus H⁺ permeability is reported here. The effective D_HCi 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 DHCI at near-neutral and alkaline pH are 4- to 10-fold lower through mucus than through aqueous films. Moreover, the pK_a values of HCO^-₃ and NH₃ (generated by urease action on urea) had a profound effect on measured D_HC1. These in vitro studies suggest that a high local concentration of NH, and HCO^-₃ within the mucus layer, generated by the action of Helicobacter pylori urease on endogeneous 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 pK_a values of HCO^-₃, and NH₃ and in extreme circumstances it may result in gastric ulcer formation.

Key Words:

• Ammonium bicarbonate
• H⁺ diffusion
• Helicobacter pylori
• mucus
• peptic ulcer
• urea
• urease