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 N a+ absorption, presumably by acidification of colonocytes and activati on of apical Na+/H+ exchangers. It is unclear whether this effect depe nds on SCFA gradients across the colonic epithelium, and, if so, why. The aim of this study was to determine (1) whether SCFAs added unilate rally to either the apical or basolateral border of the cell have simi lar effects on intracellular pH (pH(i)); (2) whether SCFA gradients al ter Na+ transport and; (3) what regulatory factors are involved in gra dient-induced Na+ transport. Methods: pH(i) was measured in intact epi thelial rabbit proximal colon using the pH-sensitive indicator 2',7'-b is(carboxyethyl)-5-(6)-carboxyfluorescein, and Na+ transport was measu red under short-circuit conditions. Results: Apical and basolateral SC FAs had equivalent effects on decreasing pH(i), but the recovery towar d baseline was more vigorous after apical SCFAs, Gradients of both pro pionate and lactate (50 mmol/L [mucosal], 0 mmol/L [serosal]) stimulat ed electroneutral Na+ absorption, which was inhibited by bicarbonate, mucosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, and Cl- remo val. However, it was not blocked by amiloride. The differential respon se to a series of pharmacological agents showed that gradient-stimulat ed transport is distinct from epinephrine-stimulated electroneutral Na + absorption. Conclusions: A physiological gradient of SCFAs across th e colonic epithelium elicits polarized effects on both pH(i) and Na+ a bsorption that may be important determinants of colonic fluid transpor t.