Carbonic anhydrase in the gastrointestinal mucus of mammals—possible protective role against carbon dioxide¹

Abstract

We show here that luminal mucus from the colon and the stomach of guinea pigs, mice and humans exhibits substantial carbonic anhydrase (CA) activity, by which the velocity of the CO₂ hydration reaction is accelerated 1000–2000-fold, approximately 1/10 of what is found in the red cell. Although this CA shares several properties with CA II, studies with CA II-deficient mice show that gastrointestinal mucus CA is not affected in these animals and thus does not appear to be CA II. We speculate that the mucus layer covering the luminal surface of gastrointestinal epithelium can, due to the presence of CA, maintain a normal tissue pCO₂ in the epithelium, even when the pCO₂ values in the lumen are much higher, as is known for stomach and colon. To test this hypothesis, we have developed a mathematical model which describes (a) diffusion of CO₂ and HCO₃⁻ across the mucus layer and (b) H⁺ transport mediated by continuous secretion of mucus, which due to its high H⁺ buffer capacity transports H⁺ by convection towards the lumen. The model predicts that continuous transport of the reaction products of CO₂ towards the lumen, by diffusion and convection, protects the epithelium against high CO₂ partial pressures in the lumen.

Introduction

It has been postulated that the apical membrane of epithelial cells in the colon and the stomach may be impermeable to NH₃ and CO₂ (Boron et al., 1994, Waisbren et al., 1994, Singh et al., 1995). Such a property of these cells would be very useful in the view of the high partial pressures of both NH₃ and CO₂ that can occur in colon as well as in stomach. A gas-impermeable apical membrane would protect the epithelial cell against the exposure to high levels of NH₃ and CO₂, thus avoiding the toxic effects of NH₃ and the acid load presented by CO₂. However, in view of the fact that lipid bilayers possess permeability for both gases, it remained entirely unclear, which special property these apical membranes might possess that renders them virtually impermeable to the two gases. More direct measurements of a relatively low permeability—certainly not an impermeability—of an epithelium have only been reported in the case of the mammalian bladder (Negrete et al., 1996).

In the present study, we report that gastrointestinal mucus possesses a surprisingly high activity of a special isoform of carbonic anhydrase. The latter may be related to the apparent impermeability towards CO₂ of the apical membranes that are covered by a thick layer of mucus. A calculation modeling the transport of CO₂ and its reaction products in the mucus layer shows that mucus carbonic anhydrase can keep the partial pressure of CO₂ on the apical epithelial membrane low although the pCO₂ in the gastrointestinal lumen is high. Thus, mucus equipped with carbonic anhydrase activity may provide an apparent barrier against CO₂ and exert a protective effect upon the epithelial cell even if the apical membrane is permeable to CO₂.