The role of HCO(3)(–) in propionate-induced anion secretion across rat caecal epithelium

Propionate, a metabolite from the microbial fermentation of carbohydrates, evokes a release of epithelial acetylcholine in rat caecum resulting in an increase of short-circuit current (I(sc)) in Ussing chamber experiments. The present experiments were performed in order to characterize the ionic mechanisms underlying this response which has been thought to be due to Cl(−) secretion. As there are regional differences within the caecal epithelium, the experiments were conducted at oral and aboral rat corpus caeci. In both caecal segments, the propionate-induced I(sc) (I(Prop)) was inhibited by > 85%, when the experiments were performed either in nominally Cl(−)- or nominally HCO(3)(−)-free buffer. In the case of Cl(−), the dependency was restricted to the presence of Cl(−) in the serosal bath. Bumetanide, a blocker of the Na(+)-K(+)-2Cl(−)-cotransporter, only numerically reduced I(Prop) suggesting that a large part of this current must be carried by an ion other than Cl(−). In the aboral caecum, I(Prop) was significantly inhibited by mucosally administered stilbene derivatives (SITS, DIDS, DNDS), which block anion exchangers. Serosal Na(+)-free buffer reduced I(Prop) significantly in the oral (and numerically also in aboral) corpus caeci. RT-PCR experiments revealed the expression of several forms of Na(+)-dependent HCO(3)(−)-cotransporters in caecum, which might underlie the observed Na(+) dependency. These results suggest that propionate sensing in caecum is coupled to HCO(3)(–) secretion, which functionally would stabilize luminal pH when the microbial fermentation leads to an increase in the concentration of short-chain fatty acids in the caecal lumen. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00424-021-02565-8.