Distension-induced secretion in the rat colon: mediation by prostaglandins and submucosal neurons

Distension of the rat colon descendens in vitro by a hydrostatic gradient induced an increase in short-circuit current (Isc). In a mucosa-submucosa preparation containing the plexus submucosus, the increase in Isc was biphasic with a half-time of about 200 s for the spontaneous returning to the baseline. The time course was monophasic in a mucosa preparation without the plexus submucosus. The increase in Isc in the mucosa-submucosa preparation was inhibited by an inhibitor of phospholipase A2, quinacrine, and by indomethacin, tetrodotoxin or atropine; each of these compounds also abolished the second phase of the response. In contrast, only indomethacin was effective in reducing the increase in Isc in the mucosa preparation. In both preparations the response to distension was inhibited by scilliroside, by replacement of Cl- with gluconate, and by administration of frusemide or the chloride channel blocker, anthracene-9-carboxylic acid. The results indicate that distension induces chloride secretion by causing the release of prostaglandins, which act indirectly, i.e. mediated by the submucosal plexus, and directly at the epithelium.