15d-Prostaglandin J2 Enhancement of Nerve Growth Factor–Induced Neurite Outgrowth Is Blocked by the Chemoattractant Receptor– Homologous Molecule Expressed on T-Helper Type 2 Cells (CRTH2) Antagonist CAY10471 in PC12 Cells

Michiyoshi Hatanaka; Norihiro Shibata; Norihito Shintani; Ryota Haba; Atsuko Hayata; Hitoshi Hashimoto; Akemichi Baba

doi:10.1254/jphs.10001SC

Short Communications

15d-Prostaglandin J₂ Enhancement of Nerve Growth Factor–Induced Neurite Outgrowth Is Blocked by the Chemoattractant Receptor– Homologous Molecule Expressed on T-Helper Type 2 Cells (CRTH2) Antagonist CAY10471 in PC12 Cells

Michiyoshi Hatanaka, Norihiro Shibata, Norihito Shintani, Ryota Haba, Atsuko Hayata, Hitoshi Hashimoto, Akemichi Baba

Author information

Michiyoshi Hatanaka
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
Norihiro Shibata
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
Norihito Shintani
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
Ryota Haba
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
Atsuko Hayata
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
Department of Experimental Disease Model, The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of Medicine, Osaka University, Japan
Hitoshi Hashimoto
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
Department of Experimental Disease Model, The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of Medicine, Osaka University, Japan
United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Japan
Akemichi Baba
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan

Keywords: chemoattractant receptor–homologous molecule expressed on T-helper type 2 cells (CRTH2), nerve growth factor (NGF), neurite outgrowth

JOURNAL FREE ACCESS

2010 Volume 113 Issue 1 Pages 89-93

DOI https://doi.org/10.1254/jphs.10001SC

View "Advance Publication" version (April 16, 2010).

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Abstract

The chemoattractant receptor–homologous molecule expressed on T-helper type 2 cells (CRTH2) is the most recently identified prostaglandin (PG) receptor for both PGD₂ and 15-deoxy-Δ^12,14-PGJ₂ (15d-PGJ₂). We examined the mechanism by which 15d-PGJ₂ enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. CAY10471 (CRTH2 antagonist) inhibited both the neurite-promotion and p38 mitogen-activated protein (MAP) kinase phosphorylation induced by 15d-PGJ₂. In contrast, 13,14-dihydro-15-keto-PGD₂(DK-PGD₂) (selective CRTH2 agonist) stimulated its phosphorylation but failed to produce neurite-promoting effects. These suggest, for the first time, the action of 15d-PGJ₂ is mediated by CRTH2, although the CRTH2 activation alone is insufficient for the underlying action.

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