Mechanisms of VIP-induced neuroprotection against neonatal excitotoxicity.
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.
Rangon
Claire-Marie
CM
INSERM U 676, Hôpital Robert Debré, 48 Blvd Sérurier, 75019 Paris, France.
Dicou
Eleni
E
Goursaud
Stéphanie
S
Mounien
Lourdes
L
Jégou
Sylvie
S
Janet
Thierry
T
Muller
Jean-Marc
JM
Lelièvre
Vincent
V
Gressens
Pierre
P
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*
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