<b>PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca</b><sup><b>2+</b></sup><b>-regulated </b><b>exocytosis </b>
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- TANAKA Saori
- Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences
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- HOSOGI Shigekuni
- Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Department of Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Japan Institute for Food Education and Health, St. Agnes’ University
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- SAWABE Yukinori
- Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
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- SHIMAMOTO Chikao
- Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences
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- MATSUMURA Hitoshi
- Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences
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- INUI Toshio
- Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Department of Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Saisei Mirai Clinics
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- MARUNAKA Yoshinori
- Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Department of Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Japan Institute for Food Education and Health, St. Agnes’ University
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- NAKAHARI Takashi
- Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Department of Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Japan Institute for Food Education and Health, St. Agnes’ University
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抄録
A PPARα (peroxisome proliferation activation receptor α) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARα activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARα (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca2+-regulated exocytosis) mediated via NO, which was abolished by GW6471, N-PLA, wortmannin, and AKT-inh. The Western blotting revealed that GW7647 phosphorylates NOS1 via phosphorylation of PI3K/Akt in antral mucous cells. The immunofluorescence examinations demonstrated that PPARα existing with NOS1 co-localizes with PI3K and Akt in the cytoplasm of antral mucous cells. ACh alone and AACOCF3, an analogue of arachidonic acid (AA), induced the NOS1 phosphorylation via PI3K/Akt to produce NO, which was inhibited by GW6471. Since AA is a natural ligand for PPARα, ACh stimulates PPARα probably via AA. In conclusion, PPARα activates NOS1 via PI3K/Akt phosphorylation to produce NO in antral mucous cells during ACh stimulation.
収録刊行物
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- Biomedical Research
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Biomedical Research 37 (3), 167-178, 2016
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