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Activation of VIP/PACAP type 2 receptor by the peptide histidine isoleucine in astrocytes influences GLAST-mediated glutamate uptake
| Content Provider | Scilit |
|---|---|
| Author | Goursaud, Stéphanie Hermans, Emmanuel Maloteaux, Jean-Marie |
| Copyright Year | 2008 |
| Description | Journal: Journal of Neurochemistry Considering the putative neuroprotective role of the vasoactive intestinal peptide (VIP) and the pituitary adenylyl cyclase-activating polypeptide (PACAP), we investigated the acute modulation of glial glutamate uptake by the structurally related peptide histidine isoleucine (PHI). Using cultures of cortical astrocytes, we demonstrated that a 6 min treatment with 1 micromol/L PHI strongly increased the d-[3H]-aspartate uptake velocity from 24.3 +/- 1.9 to 46.8 +/- 3.5 nmol/mg prot/min. This effect was found to reflect an increase in the activity of the GLAST, the predominant functional glutamate transporter in these cultures. The combination of protein kinase A and C inhibitors was effective in blocking the effect of PHI and the use of peptide antagonists contributed to demonstrate the implication of the VIP/PACAP type 2 receptor (VPAC(2)). Accordingly, G-protein activation measures and gene reporter assays revealed the expression of functional PHI-sensitive receptors in cultured astrocytes. Biotinylation/immunoblotting studies indicated that PHI significantly increased the cell surface expression of the GLAST (by 34.24 +/- 8.74 and 43.00 +/- 6.36%, when considering the 72 and 55 kDa immunoreactive proteins, respectively). Such cross-talk between PHI and glutamate transmission systems in glial cells opens attractive perspectives in neuropharmacology. |
| Ending Page | 1175 |
| Starting Page | 1165 |
| ISSN | 2573508X |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.2008.05231.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 4 |
| Volume Number | 105 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2008-05-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Biochemistry and Molecular Biology Glutamate Transporters |
| Content Type | Text |
| Resource Type | Article |