Activation of VIP/PACAP type 2 receptor by the peptide histidine isoleucine in astrocytes influences GLAST-mediated glutamate uptake

Journal of Neurochemistry
Stéphanie GoursaudEmmanuel Hermans

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 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...Continue Reading

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Citations

Apr 7, 2009·Journal of Biological Rhythms·Luciano MarpeganErik D Herzog
Jul 7, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stéphanie GoursaudEmmanuel Hermans
Jul 28, 2021·Neurochemistry International·Inês Belo do NascimentoEmmanuel Hermans

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