Prostaglandin E2 (PGE2)‐evolted chloride secretion in guinea‐pig colon is mediated by nerve‐dependent and nerve‐independent mechanisms

Conventional flux chamber and intracellular recording methods were used to investigate the effect of prostaglandin E2 on ion transport and on electrical behaviour of submucosal neurones in guinea-pig colon. In flux chamber experiments, prostaglandin E2 evoked a dose-dependent increase in short-circuit current. The response was reduced by serosal addition of bumetanide, tetrodotoxin or atropine, but not hexamethonium or piroxicam. This indicates that the response to prostaglandin E2 was mediated in part by activation of chloride secretion via submucosal neurons. Application of prostaglandin E2 to submucosal neurones evoked a depolarization of the membrane potential associated with an enhanced spike discharge which was frequently triggered by fEPSPs. The depolarizing response to prostaglandin E2 was not affected by tetrodotoxin, indicative of a direct effect of prostaglandin E2 on the impaled neurones. However, the increased spike activity was synaptically driven suggesting an additional activation of other cells. Prostaglandin E2 had no excitatory or inhibitory effect on cholinergic fast excitatory postsynaptic potentials. The study suggests that prostaglandin E2 may function as a neuromodulator to evoke nerve-mediated chloride secretion through activation of submucosal neurones. The results further indicate that prostaglandin E2 may influence mucosal function by altering electrical behaviour of submucosal neurones leading to spread of excitation throughout the plexus.