Mechanisms of acid damage to oesophageal epithelium: role of the paracellular pathway.

The mechanisms of acid damage to oesophageal epithelium are incompletely understood. In particular, it is unclear whether luminal acid enters and damages the oesophageal epithelium by traversing the paracellular and/or transcellular route. The present paper describes studies of the role of serosal bicarbonate ions (HCO3-) in oesophageal protection against acid damage, the results of which have direct implications regarding the route of H+ entry. The results indicate that HCO3- protects by buffering H+ within the intercellular compartment of the extracellular space, and that this protection can be mimicked almost completely by replacement of serosal HCO3- with HEPES (N-2-hydroxyethylpiperazine-N'-2-ethane sulphonic acid), a buffer that cannot permeate cells. These findings support the hypothesis that luminal acid damages oesophageal epithelium primarily by H+ diffusion through the paracellular pathway.