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Peroxisome proliferation activation receptor α modulation of Ca 2+ ‐regulated exocytosis via arachidonic acid in guinea‐pig antral mucous cells
Author(s) -
Sawabe Yukinori,
Shimamoto Chikao,
Sakai Akiko,
Kuwabara Hiroko,
Saad Adel H.,
Nakano Takashi,
Takitani Kimitaka,
Tamai Hiroshi,
Mori Hiroshi,
Marunaka Yoshinori,
Nakahari Takashi
Publication year - 2010
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2010.053603
Subject(s) - exocytosis , arachidonic acid , medicine , chemistry , endocrinology , prostaglandin , biology , biochemistry , secretion , enzyme
Indomethacin (IDM, 10 μ m ), not aspirin (ASA; 10 μ m ), enhanced the Ca 2+ ‐regulated exocytosis stimulated by 1 μ m acetylcholine (ACh) in guinea‐pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15 R ‐hydroperoxy‐eicosatetraenoic acid (15R‐HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R‐HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 μ m ) enhanced Ca 2+ ‐regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF 3 ), also enhanced Ca 2+ ‐regulated exocytosis, indicating that AA, not products from AA, enhances Ca 2+ ‐regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor α (PPARα), because AA is a natural ligand for PPARα. A PPARα agonist (WY14643; 1 μ m ) enhanced Ca 2+ ‐regulated exocytosis, and a PPARα blocker (MK886; 50 μ m ) abolished the enhancement of Ca 2+ ‐regulated exocytosis induced by AA, IDM, AACOCF 3 and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARα exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca 2+ ‐regulated exocytosis activated by 1 μ m ACh or 2 μ m thapsigargin alone by 25–30%. Thus, ACh stimulates AA accumulation via an [Ca 2+ ] i increase, which activates PPARα, leading to enhancement of Ca 2+ ‐regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARα enhances Ca 2+ ‐regulated exocytosis in guinea‐pig antral mucous cells.