Distension evoked mucosal secretion in human and porcine colon in vitro

PLoS One. 2023 Apr 13;18(4):e0282732. doi: 10.1371/journal.pone.0282732. eCollection 2023.

Abstract

It was suggested that intestinal mucosal secretion is enhanced during muscle relaxation and contraction. Mechanisms of mechanically induced secretion have been studied in rodent species. We used voltage clamp Ussing technique to investigate, in human and porcine colonic tissue, secretion evoked by serosal (Pser) or mucosal (Pmuc) pressure application (2-60 mmHg) to induce distension into the mucosal or serosal compartment, respectively. In both species, Pser or Pmuc caused secretion due to Cl- and, in human colon, also HCO3- fluxes. In the human colon, responses were larger in proximal than distal regions. In porcine colon, Pmuc evoked larger responses than Pser whereas the opposite was the case in human colon. In both species, piroxicam revealed a strong prostaglandin (PG) dependent component. Pser and Pmuc induced secretion was tetrodotoxin (TTX) sensitive in porcine colon. In human colon, a TTX sensitive component was only revealed after piroxicam. However, synaptic blockade by ω-conotoxin GVIA reduced the response to mechanical stimuli. Secretion was induced by tensile rather than compressive forces as preventing distension by a filter inhibited the secretion. In conclusion, in both species, distension induced secretion was predominantly mediated by PGs and a rather small nerve dependent response involving mechanosensitive somata and synapses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chlorides
  • Colon*
  • Humans
  • Intestinal Mucosa
  • Piroxicam* / pharmacology
  • Prostaglandins
  • Swine
  • Tetrodotoxin / pharmacology

Substances

  • Piroxicam
  • Tetrodotoxin
  • Prostaglandins
  • Chlorides

Grants and funding

The project was funded by NIH/SPARC (1OT2OD0248999) to M.S. and G.M.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.