Prostaglandin I(2) sensory input into the enteric nervous system during distension-induced colonic chloride secretion in rat colon.

AIM

Intestinal pressure differences or experimental distension induce ion secretion via the enteric nervous system, the sensorial origin of which is only poorly understood. This study aimed to investigate sensorial inputs and the role of afferent and interneurones in mechanically activated submucosal secretory reflex circuits.

METHODS

Distension-induced rheogenic chloride secretion was measured as increase in short-circuit current 10 min after distension (DeltaI(SC)(10); distension parameters +/- 100 microL, 2 Hz, 20 s) in partially stripped rat distal colon in the Ussing-chamber in vitro. PGE(2) and PGI(2) were measured by radioimmunoassay.

RESULTS

DeltaI(SC)(10) was 2.0 +/- 0.2 micromol h(-1) cm(-2) and could be attenuated by lobeline, mecamylamine and dimethylphenylpiperazine, indicating an influence of nicotinergic interneurones. Additionally, a contribution of afferent neurones was indicated from the short-term potentiation of DeltaI(SC)(10) by capsaicin (1 microm). As evidence for its initial event, indomethacin (1 microm) inhibited distension-induced secretion and the release of PGI(2) was directly detected after distension. Furthermore, serotoninergic mediation was confirmed by granisetron (100 microm) which was functionally localized distally to PGI(2) in this reflex circuit, as granisetron inhibited an iloprost-induced I(SC), while indomethacin did not affect serotonin-activated ion secretion.

CONCLUSIONS

Distension-induced active electrogenic chloride secretion in rat colon is mediated by a neuronal reflex circuit which includes afferent neurones and nicotinergic interneurones. It is initiated by distension-induced PGI(2) release from subepithelial cells triggering this reflex via serotoninergic 5-HT(3) receptor transmission. Functionally, this mechanism may help to protect against intestinal stasis but could also contribute to luminal fluid loss, e.g. during intestinal obstruction.