Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
Carbonic anhydrase in the gastrointestinal mucus of mammals—possible protective role against carbon dioxide1☆,
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.
Section snippets
Samples from guinea pigs
Male guinea pigs (body mass 550–700 g) from Pietsch (Hohlenberg, Germany) were used. Maintenance and treatment of the animals was as described by von Engelhardt et al. (1994). After decapitation between 08.00 and 09.00 h the large intestine was removed, cut into the different segments (caecum, proximal colon and distal colon) and rinsed with 25 mM Tris–SO4, pH 8, to remove luminal contents. Mucus samples were obtained from the second rinse of the intestinal segments with the same buffer
Specific carbonic anhydrase activity in gastrointestinal mucus
Table 1 shows the specific CA activities found in the mucus of the proximal and distal colon and the stomach of mice, guinea pigs and humans. It is apparent that in general the CA activities tend to be greater in the mucus from proximal than from distal colon where it was possible to collect the mucus samples separately from the colonic segments. The reason is not clear, but it may be related to the greater magnitude of the ion fluxes occurring in the proximal compared to the distal colon.
Discussion
What is the physiological role of the remarkably high CA activity in mucus? It is well documented that extracellular membrane-bound CA such as CA IV in many cells serves to establish rapid equilibrium between H+, HCO3− and CO2, especially in cases where H+ are transported in large amounts across the membrane. Examples are the luminal epithelial membrane of the proximal kidney tubule, across which substantial H+ fluxes via the Na+–H+ exchanger occur, or lactic acid transfer across the sarcolemma
Acknowledgements
Supported by Deutsche Forschungsgemeinschaft SFB 621/Projekt C5.
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This paper is based on a presentation given in the symposium ‘The comparative physiology of carbonic anhydrase: A tribute to Dr T.H. Maren’ which took place as part of the the American Physiological Society Meeting ‘The Power of Comparative Physiology: Evolution, Integration and Applied’, San Diego, California, USA, August 24–28, 2002. Financial support for the symposium from the Thomas H. Maren Foundation is gratefully acknowledged.
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This paper is dedicated to Professor Waldemar Moll on the occasion of his 69th birthday.