SKF83959, an Agonist of Phosphatidylinositol-Linked D1-Like Receptors, Promotes ERK12 Activation and Cell Migration in Cultured Rat Astrocytes 英文参考文献.docVIP

SKF83959,anAgonistofPhosphatidylinositol-LinkedD1- LikeReceptors,PromotesERK1/2ActivationandCell MigrationinCulturedRatAstrocytes ChaoHuang1,JingjingWu2,RujiaLiao1,WeiZhang1* 1Department of Pharmacology, School of Medicine, Nantong University, Nantong, Jiangsu, People’s Republic of China, 2Department of Internal Medicine, Suzhou KowloonHospital,Suzhou,Jiangsu,People’sRepublicofChina Abstract Extracellularsignal-regulatedkinase1/2(ERK1/2)isamemberofthemitogen-activatedproteinkinasefamily.Itcanmediate cellmigration.Classicaldopaminereceptor-mediatedERK1/2phosphorylationiswidelystudiedinneurons.Here,wereport that ERK1/2 phosphorylation is also modulated by putative phosphatidylinositol-linked D1-like receptors in cultured rat astrocytes.6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine(SKF83959),anagonist oftheputativephosphatidylinositol-linkedD1-likereceptors,wasfoundtoenhanceERK1/2phosphorylation,which then 2+ promoted the migration of cultured astrocytes. The SKF83959-induced ERK1/2 phosphorylation was found to be Ca - 2+ independentbasedonthefollowingobservations:i.chelatingintracellularCa didnotinhibitERK1/2phosphorylationand astrocyte migration; ii. blockage of the release of intracellular Ca2+ from the endoplasmic reticulum by an inhibitor of inositol1,4,5-trisphosphate(IP3)receptordidnotattenuateERK1/2phosphorylation.However,inhibitionofphospholipase C (PLC), the upstream molecule of internal Ca2+ release, disabled SKF83959’s ability to elevate the level of ERK1/2 phosphorylation. Both non-selective protein kinase C (PKC) inhibitor and PKCd selective inhibitor prevented ERK1/2 2+ phosphorylation increase and astrocyte migration, but PKCa inhibitor did not. This suggests that Ca -independent and diacylglycerol-dependent PKCd acts downstream of putative phosphatidylinositol-linked D1-like receptor activation and mediatesSKF83959-inducedelevationofERK1/2phosphorylationinordertomodulateastrocytemigration.Inconclus