Effect of short-chain fatty acids on cyclic 3′,5′-guanosine monophosphate-mediated colonic secretion

Short chain fatty acids (SCFA) prevent and reverse cyclic 3',5'-adenosine monophosphate (cAMP) but not Ca2+-mediated Cl- secretion. Mucosal [HCO3-](i) has an opposite effect on these secretagogues. We examined whether SCFA and [HCO3-](i) affect cyclic 3',5'-guanosine monophosphate (cGMP)-induced secretion. Stripped segments of male Sprague-Dawley rat (Rattus norvegicus) proximal and distal colon, and cultured T84 cells were studied in Ussing chambers, and pH(i) and [HCO3-](i) were determined. Mucosal [cGMP] was measured in proximal colon. In T84 cells, the increase in Cl- secretion (measured as I-sc) induced by mucosal 0.25 mu M Escherichia coli heat-stable enterotoxin (STa) was prevented/reversed by bilateral 50 mM Na+ butyrate (71%/73%), acetate (58%/76%), propionate (68%/73%) and (poorly metabolized) isobutyrate (80%/79%). In proximal colon in HCO, Ringer, basal Cl- secretion was not affected by [HCO3-](i) 25 mM butyrate. Mucosal 0.25 mu M STa decreased net Na+ and Cl- absorption. Bilateral but not mucosal 25 mM SCFA reversed STa-induced effects on Na+ absorption and Cl- secretion. Bilateral and mucosal 25 mM SCFA but not [HCO3-](i) prevented STa-induced Cl- secretion and increases in mucosal [cGMP]. STa did not produce Cl- secretion in distal colon. It was concluded that SCFA but not [HCO3-](i) can prevent and reverse cGMP-induced colonic Cl- secretion. (C) 1999 Elsevier Science Inc. All rights reserved.