Ionic dependency, sensitivity to transport inhibitors and signal transduction of propionate-induced anion secretion in rat caecum
Year: 2025
Type: article
Abstract: Background Although the caecum is the most important fermentation chamber in non-ruminant animals, the epithelial responses evoked by microbially produced short-chain fatty acids such as propionate are not well understood. Methods Short-circuit currents (I sc ) across rat caecum were measured in Ussing chamber experiments, where anionic conditions, transport mechanisms and underlying signaling pathways regarding propionate-induced I sc (I Prop ) were analyzed. These findings were complemented with immunofluorescence and RT-PCR. Main results I Prop was dependent on the simultaneous presence of Cl - and HCO 3 - . This contrasts with the I sc evoked by the cAMP- or Ca 2+ -dependent secretagogues, forskolin and carbachol, where replenishment of Cl - was sufficient to induce a strong increase in I sc . Blocking the cystic fibrosis transmembrane regulator (CFTR) with CFTR inh -172 inhibited I Prop in the oral caecum, whereas in the aboral caecum the additional presence of 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), an inhibitor of anion exchangers, was necessary to reduce I Prop significantly. Since propionate can activate free-fatty acid receptors type 2 (coupled to G q and G i proteins) and 3 (coupled to G i proteins), downstream signaling was further elucidated. Inhibition of G qα , phospholipase C, inositol-3,4,5-trisphosphate receptors, or phosphatidyl inositol kinases reduced I Prop significantly. Kinases of the ‘with no lysine’ family (WNK), known to mediate the switch between Cl - to HCO 3 - secretion in other cells, are also involved in propionate-induced anion secretion, since I Prop was reduced by panWNK and WNK1 inhibition. Conclusion Propionate stimulates anion secretion, probably in order to buffer the caecal luminal content, by a mechanism exhibiting a unique anion dependency different from that of other secretagogues.
Source: European Journal of Pharmacology
Institution: Justus-Liebig-Universität Gießen
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,230
OpenAlex ID: W7117139331