Abstract
Iindomethacin effects on Ca2+-regulated exocytosis activated by acetylcholine (ACh, 10 μM) were studied in guinea pig antral mucous cells using video optical microscopy. Indomethacin, which inhibits prostaglandin E2 (PGE2) synthesis, decreased the frequency of ACh-stimulated exocytotic events by 30% in a dose-dependent manner, and an inihibitor of PKA (10 μM H-89) also decreased the frequency of ACh-stimulated exocytotic events by 30%. However, the addition of PGE2 (1 μM), which accumulates cAMP via the EP4 receptor, prevented the indomethacin-induced decrease in the frequency of ACh-stimulated exocytotic events. A similar inhibition was induced by aspirin. Thus, indomethacin decreased the frequency of ACh-stimulated exocytosis by reducing PGE2 synthesis. SC560 (a COX1 inhibitor) decreased the frequency of ACh-stimulated exocytotic events by 30%, but NS389 (a COX2 inhibitor) did not. Moreover, indomethacin also decreased the frequency of exocytotic events stimulated by ionomycin. Thus, indomethacin inhibited COX1, which was stimulated by an increase in intracellular Ca2+ concentration ([ Ca2+]i). In conclusion, in antral mucous cells, ACh increases [ Ca2+]i, which stimulates exocytotic events and PGE2 release via COX1. The released PGE2 enhances the Ca2+-regulated exocytosis mediated by cAMP accumulation. The autocrine mechanism mediated by PGE2, which is inhibited by indomethacin, maintains the exocytotic events in ACh-stimulated antral mucous cells. [Jpn J Physiol 54 Suppl:S71 (2004)]
