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

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Short chain fatty acids (SCFA) prevent and reverse cyclic 3′,5′-adenosine monophosphate (cAMP) but not Ca 2+-mediated Cl − secretion. Mucosal [HCO 3 −] i has an opposite effect on these secretagogues. We examined whether SCFA and [HCO 3 −] 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 [HCO 3 −] 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 μM Escherichia coli heat-stable enterotoxin (ST a) 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 3 − Ringer, basal Cl − secretion was not affected by [HCO 3 −] i or 25 mM butyrate. Mucosal 0.25 μM ST a decreased net Na + and Cl − absorption. Bilateral but not mucosal 25 mM SCFA reversed ST a-induced effects on Na + absorption and Cl − secretion. Bilateral and mucosal 25 mM SCFA but not [HCO 3 −] i prevented ST a-induced Cl − secretion and increases in mucosal [cGMP]. ST a did not produce Cl − secretion in distal colon. It was concluded that SCFA but not [HCO 3 −] i can prevent and reverse cGMP-induced colonic Cl − secretion.