FFA3 and TRPM5 Are Involved in the Sodium Propionate‐Induced Anion Secretion in Mouse Proximal Colon

Abstract

Luminal short-chain fatty acids (SCFA) triggers cholinergic signals for anion secretion in the rodent colonic mucosa, while exact mechanisms are still unclear. Tuft cells, one of luminal chemosensing components in the intestine, expresses choline acetyltransferase (ChAT), transient receptor potential menthol 5 (TRPM5) and free fatty acid receptor 3 (FFA3). We thus examined the roles of TRPM5 and FFA3 in SCFA-induced anion secretion in mouse proximal colon. Short-circuit current (Isc) was measured in the muscle-stripped mouse proximal colonic mucosa mounted in an Ussing chamber. Sodium propionate (NaP, 10 mM, m), atropine (10 µM, s), the selective free fatty acid receptor 3 (FFA3) antagonist AR399519 (1 µM, m or s), or the TRPM5 antagonist triphenylphosphine oxide (TPPO, 1 - 300 µM, m or s) were applied to the mucosal (m) or serosal (s) baths of an Ussing chamber. Luminal NaP transiently increased Isc with atropine-sensitive manner. NaP-induced Isc increase was dose-dependently inhibited by luminal application of TPPO (IC50 0.2 µM) by 76%, while serosal TPPO had higher IC50 (53.5 µM). Luminal AR399519 inhibited NaP-induced Isc increase by 77%, while serosal AR399519 inhibited by 48%. Doublecortin-like kinase 1 (DCLK1)-positive tuft cells were scattered in the epithelium, whereas FFA3 was localized in the surface epithelial cells and in the myenteric nerves. These results suggest that tuft cell TRPM5 and epithelial cell FFA3 are both involved in the NaP-induced anion secretion in mouse proximal colon.