Neural and non-neural mediation of propionate-induced contractile responses in the rat distal colon.

Short-chain fatty acids (SCFAs), including propionate, butyrate and acetate, are fermentation products of carbohydrates in the colon. We investigated the contractile effects of SCFAs on the rat distal colon. Mechanical activity of the circular muscle in strip preparations was recorded in vitro. Propionate and butyrate concentration-dependently (10 micromol L(-1)-10 mmol L(-1)) induced rapid, large amplitude phasic contractions (the first phase) followed by tonic contractions (the second phase). Acetate itself had no effect on muscle activity, although preincubation with acetate attenuated both phases of the propionate-induced response. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT4 receptor antagonist SB-204070. The propionate-induced tonic contraction was attenuated by the cyclo-oxygenase inhibitor piroxicam. Antagonists of 5-HT1A, 5-HT2A and 5-HT3 receptors had no effect on the responses. Propionate-induced responses were not observed in mucosa-free preparations. These results suggest that propionate acts on receptors in the mucosa causing the release of 5-HT from enterochromaffin cells. 5-HT acts through 5-HT4 receptors on the endings of intrinsic primary afferent neurones that in turn activate cholinergic motor neurones that contract the circular muscle. Propionate also causes tonic contraction, via prostaglandin release, in the rat distal colon.