Abstract
Superfusion of isolated crypts from rat colon with sodium butyrate–containing solutions induced an amiloride-sensitive swelling of the cells at the upper one-third of the crypt. In HCO 3 −-containing buffer, swelling was followed by regulatory volume decrease, which was inhibited by K + and C − channel blockers and inhibitors of leukotriene synthesis. Whole-cell patch-clamp recordings revealed that butyrate induced a membrane depolarization, which was dependent on Cl − and was accompanied by an increase in membrane inward current, indicating an increase in Cl − conductance. Membrane outward (K +) current, however, behaved inconsistently, suggesting an activation of swelling-induced K + currents, but an inhibition of pH-sensitive K + currents due to the cellular acidification. Cell-attached patch-clamp recordings showed an activation of basolateral Cl − channels by butyrate. The lipoxygenase inhibitor, NDGA (nordihydroguaiaretic acid), inhibited the butyrate response and even reversed it into a slight hyperpolarization indicating that the butyrate-induced Cl − channels, but not the K + channels, are stimulated by a leukotriene. Short-chain fatty acids concentration-dependently decreased short-circuit current (Isc). The decrease in Isc was diminished by a Cl − channel blocker, NPPB (5-nitro-2-[3-phenylpropylamino]-benzoate), and a lipoxygenase inhibitor, NDGA. Butyrate stimulated the mucosa to serosa fluxes (Jms) of Na + and Cl −. The effect on J Cl ms was blocked by NPPB or NDGA. The stimulation of J Cl ms correlated with the degree of metabolism of the short-chain fatty acid. Consequently, two factors seem to be responsible for the stimulation of Cl − absorption by short-chain fatty acids: (a) the intracellular production of HCO 3 − during the oxidation of short-chain fatty acids as substrate for the apical Cl −/HCO 3 − exchanger, and (b) the activation of volume-sensitive basolateral Cl − channels.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Comparative Biochemistry and Physiology -- Part A: Physiology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.