The role of HCO3– in propionate-induced anion secretion across rat caecal epithelium

Abstract

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 (Isc) 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 Isc (IProp) was inhibited by > 85%, when the experiments were performed either in nominally Cl−- or nominally HCO3−-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 IProp suggesting that a large part of this current must be carried by an ion other than Cl−. In the aboral caecum, IProp was significantly inhibited by mucosally administered stilbene derivatives (SITS, DIDS, DNDS), which block anion exchangers. Serosal Na+-free buffer reduced IProp significantly in the oral (and numerically also in aboral) corpus caeci. RT-PCR experiments revealed the expression of several forms of Na+-dependent HCO3−-cotransporters in caecum, which might underlie the observed Na+ dependency. These results suggest that propionate sensing in caecum is coupled to HCO3– 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.

The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3− by the Porcine Colon

“…These results are understandable if one assumes that NKCC1 does not contribute much to the cinnamaldehyde response. The basolateral uptake of HCO 3 − most likely occurs via basolateral cotransporters such as NBCe1 (SLC4A4), NBCe2 (Slc4a5) or NBCn1 (Slc4a7), which mediate the cotransport of Na + and HCO 3 − , and are amply expressed by the hindgut [ 53 , 54 , 55 ]. The apical efflux of HCO 3 − should be possible through apical Cl − channels such as CFTR [ 49 , 56 , 57 ], which, like practically all of the anion channels known to date, are notoriously promiscuous.…”