AN IN-VITRO STUDY OF ENHANCED H- IMPLICATIONS FOR HELICOBACTER-PYLORI-ASSOCIATED PEPTIC-ULCERATION( DIFFUSION BY UREASE ACTION ON UREA )

The in vitro effect of urea and hydrolysis of urea by urease on mucus H+ permeability is reported here. The effective D(HCl) values indicate a strong pH dependence for H+ diffusion in both water and mucus layer s, with no apparent trend at concentrations between 1 and 50 mM urea. However, the estimated D(HCl) at near-neutral and alkaline pH are 4- t o 10-fold lower through mucus than through aqueous films. Moreover, th e pK(a) values of HCO3- and NH3 (generated by urease action on urea) h ad a profound effect on measured D(HCl). These in vitro studies sugges t that a high local concentration of NH3 and HCO3-within the mucus lay er, generated by the action of Helicobacter pylori urease on endogeneo us intragastric urea, could greatly accelerate proton flux to the surf ace epithelium by operation of a buffer shuttle. This results in enhan ced H+ permeability, particularly at pK(a) values of HCO- and NH3, and in extreme circumstances it may result in gastric ulcer formation,