Activation of VIP/PACAP type 2 receptor by the peptide histidine isoleucine in astrocytes influences GLAST-mediated glutamate uptake |
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Authors: | Goursaud Stéphanie Maloteaux Jean-Marie Hermans Emmanuel |
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Institution: | Laboratoire de Pharmacologie Expérimentale, UniversitéCatholique de Louvain, Av. Hippocrate 54.10, 1200 Brussels, Belgium |
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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 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. |
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Keywords: | astrocytes GLAST glutamate glutamate transporters PHI VPAC2 |
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