{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T06:46:44Z","timestamp":1697352404187},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T00:00:00Z","timestamp":1276128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:p>Indomethacin (IDM, 10 \u03bc<jats:sc>m<\/jats:sc>), not aspirin (ASA; 10 \u03bc<jats:sc>m<\/jats:sc>), enhanced the Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis stimulated by 1 \u03bc<jats:sc>m<\/jats:sc> acetylcholine (ACh) in guinea\u2010pig antral mucous cells. Indomethacin inhibits prostaglandin G\/H (PGG\/H) and 15<jats:italic>R<\/jats:italic>\u2010hydroperoxy\u2010eicosatetraenoic acid (15R\u2010HPETE) production from arachidonic acid (AA), while ASA inhibits PGG\/H production but accelerates 15R\u2010HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 \u03bc<jats:sc>m<\/jats:sc>) enhanced Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF<jats:sub>3<\/jats:sub>), also enhanced Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis, indicating that AA, not products from AA, enhances Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor \u03b1 (PPAR\u03b1), because AA is a natural ligand for PPAR\u03b1. A PPAR\u03b1 agonist (WY14643; 1 \u03bc<jats:sc>m<\/jats:sc>) enhanced Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis, and a PPAR\u03b1 blocker (MK886; 50 \u03bc<jats:sc>m<\/jats:sc>) abolished the enhancement of Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis induced by AA, IDM, AACOCF<jats:sub>3<\/jats:sub> and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPAR\u03b1 exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis activated by 1 \u03bc<jats:sc>m<\/jats:sc> ACh or 2 \u03bc<jats:sc>m<\/jats:sc> thapsigargin alone by 25\u201330%. Thus, ACh stimulates AA accumulation via an [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase, which activates PPAR\u03b1, leading to enhancement of Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPAR\u03b1 enhances Ca<jats:sup>2+<\/jats:sup>\u2010regulated exocytosis in guinea\u2010pig antral mucous cells.<\/jats:p>","DOI":"10.1113\/expphysiol.2010.053603","type":"journal-article","created":{"date-parts":[[2010,5,15]],"date-time":"2010-05-15T00:59:32Z","timestamp":1273885172000},"page":"858-868","source":"Crossref","is-referenced-by-count":6,"title":["Peroxisome proliferation activation receptor \u03b1 modulation of Ca<sup>2+<\/sup>\u2010regulated exocytosis via arachidonic acid in guinea\u2010pig antral mucous 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