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Stimulation of Sodium Chloride Absorption from Secreting Rat Colon by Short-Chain Fatty Acids

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Abstract

Inhibition of electroneutral NaCl absorption bycyclic adenosine monophosphate (cAMP) results in fluidmalabsorption in cholera. Short-chain fatty acids (SCFA)stimulate electroneutral NaCl absorption from the colon. The present study investigatedeffects of elevated cAMP on SCFA-stimulated NaClabsorption in rat distal colon. The effect of SCFA onfluxes of 22Na and 36Cl wasstudied under voltage-clamp conditions, in the presence and absence of secretagoguesinducing mucosal cAMP elevation [ie, theophylline,cholera toxin (CT) and forskolin]. The effect ofbutyrate concentration on Na absorption in CT- andtheophyllinetreated 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 thatCl secretion was partially inhibited. The effects ofSCFA on NaCl absorption were similar regardless of thesecretagogue used. The kinetics of butyratestimulated Na absorption were altered by theophylline andCT, which decreased Km(6.87 and 7.17,respectively, compared to 10.75 mM for control) andincreased Vmax(4.55 and 8.33 compared to 3.45 mM/eq/cm2/hr for control). cAMPproduction by colonocytes in response to secretorystimuli was significantly reduced (34.4%) by butyratebut 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 secretorydiarrhea.

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Krishnan, S., Ramakrishna, B.S. & Binder, H.J. Stimulation of Sodium Chloride Absorption from Secreting Rat Colon by Short-Chain Fatty Acids. Dig Dis Sci 44, 1924–1930 (1999). https://doi.org/10.1023/A:1018871412748

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  • DOI: https://doi.org/10.1023/A:1018871412748