Stimulation of sodium chloride absorption from secreting rat colon by short-chain fatty acids

Abstract

Inhibition of electroneutral NaCl absorption by cyclic adenosine monophosphate (cAMP) results in fluid malabsorption in cholera. Short-chain fatty acids (SCFA) stimulate electroneutral NaCl absorption from the colon. The present study investigated effects of elevated cAMP on SCFA-stimulated NaCl absorption in rat distal colon. The effect of SCFA on fluxes of ²²Na and ³⁶Cl was studied under voltage-clamp conditions, in the presence and absence of secret agogues inducing mucosal cAMP elevation [ie, theophylline,cholera toxin (CT) and forskolin]. The effect ofbutyrate concentration on Na absorption in CT- and theophylline treated mucosa was compared with control normal mucosa. cAMP was measured in isolated colonocytes in thepresence of secretagogues with and without SCFA using aradioassay method. All secretagogues were noted to inhibit net Na absorption and to induce net Clsecretion. In the presence of SCFA, net Na absorptionwas normal, and net Cl secretion was partly reversed.The flux data indicated that NaCl absorption from secreting colon was stimulated by SCFA and that Cl secretion was partially inhibited. The effects of SCFA on NaCl absorption were similar regardless of the secret agogue used. The kinetics of butyrate stimulated Na absorption were altered by the ophylline and CT, which decreased Km(6.87 and 7.17,respectively, compared to 10.75 mM for control) and increased V_max(4.55 and 8.33 compared to 3.45 mM/eq/cm²/hr for control). cAMP production by colonocytes in response to secretory stimuli was significantly reduced (34.4%) by butyrate but not by acetate or propionate. In conclusion, SCFA-stimulated Na absorption is up-regulated by cAMP and maybe an absorptive pathway that can be utilized in thetherapy of cholera. Effects of butyrate on cAMPgeneration are also likely to be useful in secretory diarrhea.