EP1 and EP4 receptors mediate exocytosis evoked by prostaglandin E-2 in guinea-pig antral mucous cells

Effects of prostaglandin E2 (PGE(2)) on exocytosis of mucin were studied in mucous cells isolated from guinea-pig antrum using video-microscopy. Stimu lation with PGE2 elicited a sustained increase in the frequency of exocytot ic events in a dose-dependent manner, which was under regulation by both Ca 2+ and cAMP. Stimulation with a selective prostanoid EP4 receptor agonist ( ONO-AEI-329, 10 mum), which activates cAMP signals, elicited a sustained in crease in the frequency of exocytotic events (30% of that evoked by 1 mum P GE(2)). Stimulation with an EP1 agonist (17-P-T-PGE(2), 1 mum), which activ ates Ca2+ signals, increased the frequency of exocytotic events to a lesser extent (5 % of that evoked by 1 mum PGE(2)), while addition of an EP1 anta gonist (ONO-8713, 10 mum) decreased the frequency of exocytotic events (app roximately 40% of that evoked by 1 mum PGE(2)). However, addition of the EP 1 agonist potentiated the frequency of exocytotic events evoked by the EP4 agonist or forskolin (which elevates cAMP levels) and increased the sensiti vity of the exocytotic events to forskolin. These results suggest that the Ca2+ signal activated via the EP1 receptor potentiates the cAMP-regulated e xocytotic events activated via the EP4 receptor during PGE2 stimulation, by increasing the sensitivity of the exocytotic response to cAMP. In conclusi on, exocytotic events in PGE(2)-stimulated antral mucous cells were regulat ed by interactions between EP1 and EP4 receptors.