Title

Antagonism Of Group I Metabotropic Glutamate Receptors And Plc Attenuates Increases In Inositol Trisphosphate And Reduces Reactive Gliosis In Strain-Injured Astrocytes

Keywords

GFAP; Intracellular free calcium; IP 3; Reactive astrocytes; TBI

Abstract

We have previously found that in vitro traumatic injury uncouples IP 3-mediated intracellular free calcium ([Ca2+] i) signaling in astrocytes (Rzigalinski et al., 1998; Floyd et al., 2001). Since Group I metabotropic glutamate receptors (mGluRs) are coupled to IP3-mediated Ca2+ signaling, we investigated their role in the in vitro strain injury of cultured astrocytes. Astrocytes grown on Silastic membranes were labeled with 3H-myo-inositol and strain (stretch)-injured. Cells injured in the presence of LiCl to prevent inositol phosphate metabolism were acid extracted and inositol phosphates (IP x) isolated using anion exchange columns. Reactive gliosis was assessed as increased glial fibrillary acidic protein immunoreactivity (GFAP-IR). Pre- but not post-injury administration of (RS)-1-aminoindan-15-decarboxylic acid (AIDA) or (S)-4-carboxy-3-hydroxyphenylglycine (S4CH3HPG), both group I mGluR antagonists, attenuated injury-induced increases in IPx. Injury increased GFAP-IR in astrocytes at 24 and 48 h post injury, which was reduced or blocked by AIDA or inhibition of phospholipase C (PLC) with U73122. These findings suggest that strain injury activates Group I mGluRs, causing aberrant IP x production and uncoupling of the PLC signaling pathway. Changes in this signaling pathway may be related to induction of reactive gliosis. Additionally, our results suggest a complex physical coupling between G protein receptor, PLC, and IP3 receptor, in support of the conformational coupling model.

Publication Date

2-1-2004

Publication Title

Journal of Neurotrauma

Volume

21

Issue

2

Number of Pages

205-216

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1089/089771504322778668

Socpus ID

1242343630 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/1242343630

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