Received October 6, 2005
Revised October 17, 2005
Accepted after revision November 1, 2005

¹ Osaka Medical College

^* To whom correspondence should be addressed. E-mail: takan{at}art.osaka-med.ac.jp.

	Abstract

Ca²⁺-regulated exocytosis is enhanced by an autocrine mechanism via the PGE₂/cAMP pathway in antral mucous cells of guinea pigs. The inhibition of the PGE₂/cAMP pathway by H-89 (an inhibitor of protein kinase A (PKA)) or aspirin (ASA, an inhibitor of cyclooxygenase (COX)) decreased the frequency of ACh-stimulated exocytotic events by 60 %. Indomethacin (IDM, an inhibitor of COX), however, decreased the frequency of ACh-stimulated exocytotic events only by 30 %. Moreover, IDM increased the frequency of ACh-stimulated exocytotic events by 50 % in H-89-treated or ASA-treated cells. IDM inhibits the synthesis of PGG/H and 15R-HPETE, while ASA inhibits only the synthesis of PGG/H. Thus, IDM may accumulate AA. AACOCF₃ or ACA (inhibitors of phospholipase A2 (PLA2)), which inhibits arachidonic acid (AA) synthesis, decreased the frequency of ACh-stimulated exocytotic events by 60 %. IDM, however, did not increase the frequency in AACOCF₃-treated cells. AA increased the frequency of ACh-stimulated exocytotic events in AACOCF₃- or ASA-treated cells, similar to IDM in ASA- and H-89-treated cells. Moreover, in the presence of AA, IDM did not increase the frequency of ACh-stimulated exocytotic events in ASA-treated cells. The PGE₂ release from antral mucosa indicates that inhibition of PLA₂by ACA inhibits the AA accumulation in unstimulated and ACh-stimulated antral mucosa. The dose-response study of AA and IDM demonstrated that the concentration of intracellular AA accumulated by IDM is less than 100 nM. In conclusion, IDM modulates the ACh-stimulated exocytosis via AA accumulation in antral mucous cells.

Key Words: Acetylcholine, Arachidonic acid, Exocytosis

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