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

Abstract

Abstract Conventional flux chamber and intracellular recording methods were used to investigate the effect of prostaglandin E 2 on ion transport and on electrical behaviour of submucosal neurones in guinea‐pig colon. In flux chamber experiments, prostaglandin E 2 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 E 2 was mediated in part by activation of chloride secretion via submucosal neurons. Application of prostaglandin E 2 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 E 2 was not affected by tetrodotoxin, indicative of a direct effect of prostaglandin E 2 on the impaled neurones. However, the increased spike activity was synaptically driven suggesting an additional activation of other cells. Prostaglandin E 2 had no excitatory or inhibitory effect on cholinergic fast excitatory postsynaptic potentials. The study suggests that prostaglandin E 2 may function as a neuromodulator to evoke nerve‐mediated chloride secretion through activation of submucosal neurones. The results further indicate that prostaglandin E 2 may influence mucosal function by altering electrical behaviour of submucosal neurones leading to spread of excitation throughout the plexus.