SKF83959, an Agonist of Phosphatidylinositol-Linked D1-Like Receptors, Promotes ERK1/2 Activation and Cell Migration in Cultured Rat Astrocytes

Abstract

Extracellular signal-regulated kinase 1/2 (ERK1/2) is a member of the mitogen-activated protein kinase family. It can mediate cell migration. Classical dopamine receptor-mediated ERK1/2 phosphorylation is widely studied in neurons. Here, we report that ERK1/2 phosphorylation is also modulated by putative phosphatidylinositol-linked D(1)-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), an agonist of the putative phosphatidylinositol-linked D(1)-like receptors, was found to enhance ERK1/2 phosphorylation, which then promoted the migration of cultured astrocytes. The SKF83959-induced ERK1/2 phosphorylation was found to be Ca(2+)-independent based on the following observations: i. chelating intracellular Ca(2+) did not inhibit ERK1/2 phosphorylation and astrocyte migration; ii. blockage of the release of intracellular Ca(2+) from the endoplasmic reticulum by an inhibitor of inositol 1,4,5-trisphosphate (IP3) receptor did not attenuate ERK1/2 phosphorylation. However, inhibition of phospholipase C (PLC), the upstream molecule of internal Ca(2+) release, disabled SKF83959's ability to elevate the level of ERK1/2 phosphorylation. Both non-selective protein kinase C (PKC) inhibitor and PKCδ selective inhibitor prevented ERK1/2 phosphorylation increase and astrocyte migration, but PKCα inhibitor did not. This suggests that Ca(2+)-independent and diacylglycerol-dependent PKCδ acts downstream of putative phosphatidylinositol-linked D(1)-like receptor activation and mediates SKF83959-induced elevation of ERK1/2 phosphorylation in order to modulate astrocyte migration. In conclusion, our results demonstrate that SKF83959-induced increases in ERK1/2 phosphorylation and astrocyte migration are dependent on PLC-PKCδ signals. This might help us to further understand the functions of the putative phosphatidylinositol-linked D(1)-like receptors in the nervous system.

DOI: 10.1371/journal.pone.0049954

Extracted Key Phrases

7 Figures and Tables

05010020132014201520162017
Citations per Year

118 Citations

Semantic Scholar estimates that this publication has 118 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Huang2012SKF83959AA, title={SKF83959, an Agonist of Phosphatidylinositol-Linked D1-Like Receptors, Promotes ERK1/2 Activation and Cell Migration in Cultured Rat Astrocytes}, author={Chao Huang and Jingjing Wu and Rujia Liao and Wei Zhang}, booktitle={PloS one}, year={2012} }