Free fatty acids (FFAs) are not only an important source of energy but they also play key roles in regulating various physiological responses. FFAs including short-chain fatty acids (SCFAs) have recently been demonstrated to act as ligands of several G-protein-coupled receptors (GPCRs) (FFA1, FFA2, FFA3, GPR84 and GPR120). FFA1 and GPR120 are activated by medium- and long chain fatty acids. GPR84 is activated by mediam-chain, but not long chain FFAs. On the other hand, FFA2 and FFA3 are both activated by SCFAs. Tissue distribution studies have indicated that FFA2 and FFA3 function as chemical sensors in the colon. For the involvement of SCFAs in the regulation of colonic motility, propionate and butyrate concentration- -dependently induced phasic and tonic contractions in rat colonic circular muscle. The responses were not observed in mucosal free preparation. Thus, FFA2 and FFA3 are important molecular devices to monitor the chemical composition in colonic lumen. For the local function of SCFAs, it should be stressed that individual SCFA has different mode of actions on colonic smooth muscles. These different effects may be due to the relative contribution of FFA2 and FFA3 on the control of intestinal muscle activity. In this article, we have reviewed the expression and functions of these molecules, especially FFA2 and FFA3 on the regulation of colonic motility.
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