Effects of the inflammatory mediator prostaglandin D₂ on submucosal neurons and secretion in guinea pig colon

Conventional flux chamber and intracellular recording methods were used to investigate the mode of action of prostaglandin D₂ (PGD₂) on ion transport in muscle-stripped segments of guinea pig colon and on colonic submucosal ganglion cells. Application of PGD₂ resulted in a dose-dependent increase in short-circuit current that was reduced by serosal addition of bumetanide, tetrodotoxin, atropine, or piroxicam, but not hexamethonium. Application of PGD₂ to submucosal neurons evoked a depolarization of the membrane potential that was associated with an enhanced spike discharge. In AH/type 2 neurons, postspike afterhyperpolarizations were reduced in amplitude and duration. The depolarizing responses to PGD₂ were not affected by tetrodotoxin, indicative of a direct effect of PGD₂ on the impaled neurons. Whereas fast excitatory postsynaptic potentials (EPSPs) were not affected by PGD₂, slow EPSPs were reduced by a presynaptic effect, indicating presynaptic suppression of noncholinergic neurotransmitter release. The study demonstrates that PGD₂ acts as a neuromodulator to evoke nerve-mediated chloride secretion, predominantly through activation of cholinergic submucosal neurons. The results further indicate that PGD₂ released from lamina propria immune cells during antigenic stimulation may influence mucosal function by altering electrical behavior of submucosal neurons.