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

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-Δ12,14-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. © 2010 The Japanese Pharmacological Society.