Titre
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) potentiate the glutamate-evoked release of arachidonic acid from mouse cortical neurons. Evidence for a cAMP-independent mechanism.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Stella, N.
Auteure/Auteur
Magistretti, P.J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
1996
Volume
271
Numéro
39
Première page
23705
Dernière page/numéro d’article
23710
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
Glutamatergic neurotransmission is associated with release of arachidonic acid (AA) from membrane phospholipids of both neurons and astrocytes. Since free AA has been shown to enhance glutamate-mediated synaptic transmission, it can be postulated that glutamate release and AA formation constitute a positive feed-back mechanism for sustained excitatory neurotransmission. In the present study, we examined whether the glutamate-evoked release of AA could be modulated by peptides. Using mouse cortical neurons in primary cultures, we show that the release of AA evoked by glutamate is potentiated by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide (PACAP). This effect is mediated through the activation of PACAP I receptors. However, several arguments show that this potentiating mechanism does not involve the cAMP/PKA pathway. 1) Increasing intracellular cAMP by either cholera toxin, forskolin, or 8-Br-cAMP treatments does not affect the glutamate-evoked release of AA; 2) potentiation of the glutamate response by PACAP is not prevented by the PKA inhibitor 8-Br-Rp-cAMPS. Also, an involvement of the phospholipase C protein kinase C pathways is unlikely since inhibitors of both phospholipase C (i.e. U-73122) and protein kinase C (i.e. Ro 31-8220) do not affect the potentiation of the glutamate response by PACAP. These observations indicate an effect mediated by PACAP I receptors, which does not involve the second messenger pathways classically associated with activation of this type of receptors. Furthermore, results indicate that this potentiating mechanism mediated by PACAP I receptor acts at a level downstream of the glutamate receptor-mediated calcium influx.
Sujets
PID Serval
serval:BIB_5192
PMID
Date de création
2007-11-19T11:41:17.798Z
Date de création dans IRIS
2025-05-20T18:02:59Z