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ACh‐stimulated exocytosis enhanced by arachidonic acid in guinea pig antral mucous cells: cGMP accumulation via PPARα
Author(s) -
Nakahari Takashi,
Shimamoto Chikao
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1318-a
Subject(s) - exocytosis , arachidonic acid , medicine , endocrinology , chemistry , stimulation , acetylcholine , nitric oxide , microbiology and biotechnology , biology , biochemistry , secretion , enzyme
Arachidonic acid (AA, 10 nM – 2 μM) enhanced Ca2+‐regulated exocytosis in acetylcholine (ACh) stimulated antral mucous cells of guinea pig. The enhancement in ACh‐stimulated exocytosis induced by AA was not mediated via PGE2 accumulation. The AA actions were inhibited by MK886 (50 μM, an inhibitor of by peroxisome proliferation activation receptor ? (PPAR?), and were mimicked by PPAR? agonists (Eicosatetraynoic acid (ETYA) and WY14643). The enhancement of ACh‐stimulated exocytosis induced by AA, ETYA and WQY14643 was eliminated by a PKG inhibitor (Rp8BrPET‐cGMPS) and was mimicked by 8Br‐cGMP. Nitro‐L‐arginine methyl ester (L‐NAME) also inhibited the enhancement induced by AA, ETYA and WY14643, and 1‐Hydroxy‐2‐oxo‐3‐(N‐ethyl‐2‐aminoethyl)‐3‐ethyl‐1‐triazene (NOC‐12) enhanced ACh‐stimulated exocytosis similar to AA, ETYA and WY14643, which was inhibited by Rp8BrPET‐cGMPS. AA, ETYA or WY14643 did not increase intracellular Ca2+ concentration ([Ca2+]i) and did not enhance ACh‐stimulated increases in [Ca2+]i. Measurements of cGMP contents in antral mucosa demonstrated that stimulation with ACh, AA and PPAR? agonists stimulate cGMP accumulation, which is inhibited by MK886 and L‐NAME. In conclusion, in ACh‐stimulated antral mucous cells, AA accumulated stimulates PPAR?, which activates the NO/cGMP cascade, and PKG activated by cGMP enhances Ca2+‐regulated exocytosis in antral mucous cells by increasing number of the primed granule.μ μ μ μ μ