Activation of VIP/PACAP type 2 receptor by the peptide histidine isoleucine in astrocytes influences GLAST-mediated glutamate uptake.
(2008) Journal of Neurochemistry — Vol. 105, n° 4, p. 1165-1175 (2008)
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- Abstract
- 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 mumol/L PHI strongly increased the d-[(3)H]-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.
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Goursaud, S., Maloteaux, J.-M., & 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(4), 1165-1175. https://doi.org/10.1111/j.1471-4159.2008.05231.x (Original work published 2008)