The relationship between the effects of short‐chain fatty acids on intestinal motility in vitro and GPR43 receptor activation

Abstract The G protein-coupled receptors, GPR41 andGPR43, are activated by short-chain fatty acids(SCFAs), with distinct rank order potencies. Thisstudy investigated the possibility that SCFAs modu-late intestinal motility via these receptors. LuminalSCFA concentrations within the rat intestine weregreatest in the caecum (c. 115 mmol L )1 ) and prox-imal colon. Using similar concentrations (0.1–100 mmol L )1 ), SCFAs were found to inhibit electric-ally evoked, neuronally mediated contractions of ratdistal colon, possibly via a prejunctional site of action;this activity was independent of the presence orabsence of the mucosa. By contrast, SCFAs reducedthe amplitude but also reduced the threshold andincreased the frequency of peristaltic contractions inguinea-pig terminal ileum. In each model, the rank-order of activity was acetate (C2) propionate (C3) butyrate (C4) > pentanoate (C5) formate (C1), con-sistent with activity at the GPR43 receptor. GPR43mRNA was expressed throughout the rat gut, withhighest levels in the colon. However, the ability ofSCFAs to inhibit neuronally mediated contractions ofthe colon was similar in tissues from wild-type andGPR43 gene knockout mice, with identical rank-orders of potency. In conclusion, SCFAs can modulateintestinal motility, but these effects can be inde-pendent of the GPR43 receptor.Keywords GPR43)/), GPR43+/+, peristalsis, short-chain fatty acids.