Effects of short chain fatty acids on colonic Na+ absorption and enzyme activity

Short chain fatty acids (SCFA) stimulate colonic Na+ absorption and inhibit cAMP and cGMP-mediated Cl- secretion. It is uncertain whether SCFA have eq uivalent effects on absorption and whether SCFA inhibition of Cl- secretion involves effects on mucosal enzymes. Unidirectional Na+ fluxes were measur ed across stripped colonic segments in the Ussing chamber. Enzyme activity was measured in cell fractions of scraped colonic mucosa. Mucosal 50 mM ace tate, propionate, butyrate and poorly metabolized isobutyrate stimulated pr oximal colon Na+ absorption equally (300%). Neither 2-bromo-octanoate, an i nhibitor of beta -oxidation, nor carbonic anhydrase inhibition affected thi s stimulation. All SCFA except acetate stimulated distal colon Na+ absorpti on 200%. Only one SCFA affected proximal colon cGMP phosphodiesterase (PDE) (18% inhibition by 50 mM butyrate). Ail SCFA at 50 mM stimulated distal co lon cAMP PDE (24-43%) and decreased forskolin-stimulated mucosal cAMP conte nt. None of the SCFA affected forskolin-stimulated adenylyl cyclase in dist al colon or STa-stimulated guanylyl cyclase in proximal colon. Na+-K+-ATPas e in distal colon was inhibited 23-51% by the SCFA at 50 mM. We conclude th at all SCFA (except acetate in distal colon) stimulate colonic Na+ absorpti on equally, and the mechanism does not involve mucosal SCFA metabolism or c arbonic anhydrase. SCFA inhibition of cAMP-mediated secretion may involve S CFA stimulation of PDE and inhibition of Na+-K+-ATPase. (C) 2001 Elsevier S cience Inc. All rights reserved.