EFFECTS OF THE INFLAMMATORY MEDIATOR PROSTAGLANDIN D-2 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 D-2 (PGD(2)) on ion transport in muscle-stripped segments of guinea pig colon and on colonic submucosal ganglion cells. Application of PGD(2) 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 PGD(2) 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 PGD(2) were not affected by tetrodotoxin, indicative of a direct effect of PGD(2) on the impaled neurons. Whereas fast excitatory postsynaptic potentials (EPSPs) were not affected by PGD(2), slow EPSPs were reduced by a presynaptic effect, indicating presynaptic suppression of noncholinergic neurotransmitter release. The study demonstrates that PGD(2) acts as a neuromodulator to evoke nerve-mediated chloride secretion, predominantly through activation of cholinergic submucosal neurons. The results further indicate that PGD(2) released from lamina propria immune cells during antigenic stimulation may influence mucosal function by altering electrical behavior of submucosal neurons.