IN-VITRO CONTRACTILE EFFECTS OF SHORT-CHAIN FATTY-ACIDS IN THE RAT TERMINAL ILEUM

Short chain fatty acids (SCFAs), produced in the gut by bacterial ferm entation of carbohydrates, change intestinal motility by mechanisms as yet unknown. This study examined the mechanism(s) of action of SCFAs on contractility using isolated rat terminal ileum segments and isolat ed ileal smooth muscle cells. Strip contractions were recorded under i sometric conditions. Intracellular calcium concentration ([Ca2+]i) was measured in single cells loaded with indo-1 penta-acetoxymethyl ester (indo-1 AM). SCFAs (10(-9) to 10(-2) mol/l) induced concentration dep endent contractions. The effect was not different among the individual SCFAs. Exogenous acids (namely tartaric and citric acids) caused simi lar responses as SCFAs, whereas sodium acetate had no effect. The cont raction was not blocked by tetrodotoxin, atropine or hexamethonium, sh owing that it was not mediated through a cholinergic pathway. Moreover , removal of the mucosa or addition of procaine (a local anaesthetic) to the bath did not change the SCFA induced contraction, while verapam il (a calcium-channel antagonist) completely suppressed it. In additio n, application of SCFAs to isolated heal myocytes evoked peaks in [Ca2 +]i inhibited by D 600 (a blocker of voltage dependent calcium channel s). Taken together, these results suggest that the contractile respons e stimulated by SCFAs in the rat terminal ileum could result from an a cid sensitive calcium dependent myogenic mechanism.