title: Mechanisms of VIP-induced neuroprotection against neonatal excitotoxicity.
abstract: Two VIP receptors, shared with a similar affinity by pituitary adenylate cyclase-activating polypeptide (PACAP), have been cloned: VPAC1 and VPAC2. PHI binds to these receptors with a lower affinity. We previously showed that VIP protects against excitotoxic white matter damage in newborn mice. This article aimed to determine the receptor involved in VIP-induced neuroprotection. VIP effects were mimicked with a similar potency by VPAC2 agonists and PHI but not by VPAC1 agonists, PACAP 27 or PACAP 38. VIP neuroprotective effects were lost in mice lacking VPAC2 receptor. In situ hybridization confirmed the presence of VPAC2 mRNA. These data suggest that, in this model, VIP-induced neuroprotection is mediated by VPAC2 receptors. The pharmacology of this VPAC2 receptor seems unconventional as PACAP does not mimic VIP effects and PHI acts with a comparable potency.
authors.affiliation: INSERM U 676, Hôpital Robert Debré, 48 Blvd Sérurier, 75019 Paris, France.
authors.forename: Claire-Marie
authors.initials: CM
authors.lastname: Rangon
authors.forename: Eleni
authors.initials: E
authors.lastname: Dicou
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Goursaud
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mounien
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jégou
authors.forename: Thierry
authors.initials: T
authors.lastname: Janet
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Muller
authors.forename: Vincent
authors.initials: V
authors.lastname: Lelièvre
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D009498:Neurotoxins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide