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.
The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is the most recently identified prostaglandin (PG) receptor for both PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We examined the mechanism by which 15d-PGJ(2) 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-PGJ(2). In contrast, 13,14-dihydro-15-keto-PGD(2 )(DK-PGD(2)) (selective CRTH2 agonist) stimulated its phosphorylation but failed to produce neurite-promoting effects. These suggest, for the first time, the action of 15d-PGJ(2) is mediated by CRTH2, although the CRTH2 activation alone is insufficient for the underlying action.
Hatanaka
Michiyoshi
M
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Shibata
Norihiro
N
Shintani
Norihito
N
Haba
Ryota
R
Hayata
Atsuko
A
Hashimoto
Hitoshi
H
Baba
Akemichi
A
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000819:agonists* / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011971:Receptors, Immunologic / Q000819:agonists / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C477819:15-deoxyprostaglandin J2; C533609:CAY 10471; D002227:Carbazoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C034832:13,14-dihydro-15-ketoprostaglandin D2; D020932:Nerve Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor