The Ca2+ –regulated Exocytosis Enhanced by Arachidonic Acid/PPARα in Guinea– pig Antral Mucous Cells

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  • Tanaka Saori
    Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences
  • Nakahari Takashi
    Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine Graduate School of Medical Science

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Other Title
  • 胃幽門腺粘液開口放出のアラキドン酸/PPARαによる増強
  • イ ユウモンセン ネンエキ カイコウ ホウシュツ ノ アラキドンサン/PPARa ニ ヨル ゾウキョウ

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Abstract

In antral mucous cells, Ca2+–regulated exocytosis activated by acetylcholine (ACh) consists of a transient peak (initial phase) followed by a second slower decline (late phase). GW7647 (a PPARα agonist) enhanced the initial phase. GW6471 (a PPARα antagonist) abolished the GW7647–induced-enhancement of initial phase, but it produced the delayed transient increase in the late phase. Moreover, it also decreased the initial phase and produced the transient increase during stimulation with ACh alone. A similar transient increase in the late phase was evoked by PKG inhibitor (Rp8BrPETcGMPS), and was induced by cAMP accumulation via inhibition of cGMP–dependent PDE2. The effects of GW7647 were mimicked by arachidonic acid (a natural ligand of PPARα). Rp8BrPETcGMPS or a NOS1 inhibitor also abolished the GW7647–induced–enhancement of initial phase, but produced the transient increase in the late phase. ACh and GW7647 stimulated NO production and cGMP accumulation in antral mucosae. NOS1 and PPARα co–localized in antral mucous cells. In conclusion, during ACh stimulation, AA stimulates PPARα followed by NO accumulation via NOS1 leading to cGMP accumulation, which increases the Ca2+–regulated exocytosis in antral mucous cells.

Journal

  • MEMBRANE

    MEMBRANE 40 (5), 272-277, 2015

    THE MEMBRANE SOCIETY OF JAPAN

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