Activation of VIP/PACAP type 2 receptor by the peptide histidine isoleucine in astrocytes influences GLAST-mediated glutamate uptake
Article first published online: 13 JAN 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 105, Issue 4, pages 1165–1175, May 2008
How to Cite
Goursaud, S., Maloteaux, J.-M. and Hermans, E. (2008), Activation of VIP/PACAP type 2 receptor by the peptide histidine isoleucine in astrocytes influences GLAST-mediated glutamate uptake. Journal of Neurochemistry, 105: 1165–1175. doi: 10.1111/j.1471-4159.2008.05231.x
- Issue published online: 13 JAN 2008
- Article first published online: 13 JAN 2008
- Received September 11, 2007; revised manuscript received December 14, 2007; accepted December 20, 2007.
- glutamate transporters;
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 μmol/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 (VPAC2). 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.