Short-chain fatty acids have polarized effects on sodium transport and intracellular pH in rabbit proximal colon

Background & Aims: Short-chain fatty acids (SCFAs) stimulate colonic Na+ absorption, presumably by acidification of colonocytes and activation of apical Na+/H+ exchangers. It is unclear whether this effect depends on SCFA gradients across the colonic epithelium, and, if so, why. The aim of this study was to determine (1) whether SCFAs added unilaterally to either the apical or basolateral border of the cell have similar effects on intracellular pH (pH(i)); (2) whether SCFA gradients alter Na+ transport and; (3) what regulatory factors are involved in gradient-induced Na+ transport. Methods: pH(i) was measured in intact epithelial rabbit proximal colon using the pH-sensitive indicator 2',7'-bis(carboxyethyl)-5-(6)-carboxyfluorescein, and Na+ transport was measured under short-circuit conditions. Results: Apical and basolateral SCFAs had equivalent effects on decreasing pH(i), but the recovery toward baseline was more vigorous after apical SCFAs, Gradients of both propionate and lactate (50 mmol/L [mucosal], 0 mmol/L [serosal]) stimulated electroneutral Na+ absorption, which was inhibited by bicarbonate, mucosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, and Cl- removal. However, it was not blocked by amiloride. The differential response to a series of pharmacological agents showed that gradient-stimulated transport is distinct from epinephrine-stimulated electroneutral Na+ absorption. Conclusions: A physiological gradient of SCFAs across the colonic epithelium elicits polarized effects on both pH(i) and Na+ absorption that may be important determinants of colonic fluid transport.