Faculty Bibliography

We previously reported that systemic pH and HCO3 concentration affect ileal water and electrolyte absorption. To determine whether these effects could influence an ongoing secretory process, we measured transport in ileal loops exposed to either saline or 50-75 micrograms cholera toxin in mechanically ventilated Sprague-Dawley rats anesthetized with pentobarbital sodium. The effects of acute respiratory and metabolic acidosis and alkalosis were then examined. Decreases in systemic pH during respiratory acidosis caused equivalent increases in net water (54 +/- 8 microliters . cm-1 . h-1) and Na absorption (7 +/- 1 mu eq . cm- . h-1) and smaller increases in Cl absorption in cholera toxin compared with saline loops. These increases reversed the net secretion of these ions observed during alkalemia in the cholera toxin loops to net absorption. Metabolic acidosis and alkalosis and respiratory compensation of systemic pH of these metabolic disorders also altered cholera toxin-induced secretion in a direction consistent with the pH change. The increase in net HCO3 secretion caused by cholera toxin was unaffected by the respiratory disorders and did not vary with the HCO3 concentration in the metabolic disorders. These findings suggest that the systemic acid-base disorders that characterize intestinal secretory states may themselves alter intestinal absorptive function and fluid losses

We examined the role of carbonic anhydrase activity in intestinal transport by measuring the effect of systemic pH and PCO2 on electrolyte transport in the presence and absence of luminal acetazolamide. Adult Sprague-Dawley rats were anesthetized, and ileal and colonic segments were perfused with Ringer solution that was acetazolamide-free or that contained 0.1 mM sodium acetazolamide. Consecutive states of acute respiratory alkalosis and acidosis were created by changing the inspired CO2 from 0% (room air) to 8% CO2. In the ileum, acetazolamide perfusion did not affect the increment in net sodium and chloride absorption caused by a reduction in systemic pH. Mucosal carbonic anhydrase activity in this segment was measurable, although very low. In both the ascending and descending colon, acetazolamide perfusion reduced the increment in net sodium absorption caused by an increase in systemic PCO2. In addition, acetazolamide increased the chloride absorptive response to PCO2 in the ascending colon but did not affect the chloride response at all in the descending colon. Colonic mucosal carbonic anhydrase exhibited a proximal-to-distal gradient of activity: levels in the ascending colon were severalfold greater than in the descending colon. These findings suggest a functional role for carbonic anhydrase in mediating the colonic but not the ileal absorptive response to changes in systemic acid-base balance