RGD Reference Report - Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I. - Rat Genome Database

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Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I.

Authors: Pedersen, WA  Wan, R  Zhang, P  Mattson, MP 
Citation: Pedersen WA, etal., J Neurosci 2002 Jan 15;22(2):404-12.
RGD ID: 70397
Pubmed: PMID:11784785   (View Abstract at PubMed)
PMCID: PMC6758668   (View Article at PubMed Central)

Urocortin and urocortin II are members of the corticotropin-releasing hormone (CRH) family of neuropeptides that function to regulate stress responses. Two high-affinity G-protein-coupled receptors have been identified that bind CRH and/or urocortin I and II, designated CRHR1 and CRHR2, both of which are present in hippocampal regions of mammalian brain. The hippocampus plays an important role in regulating stress responses and is a brain region in which neurons are vulnerable during disease and stress conditions, including cerebral ischemia, Alzheimer's disease, and anxiety disorders. Here we report that urocortin exerts a potent protective action in cultured rat hippocampal neurons with concentrations in the range of 0.5-5.0 pm, increasing the resistance of the cells to oxidative (amyloid beta-peptide, 4-hydroxynonenal, ferrous sulfate) and excitotoxic (glutamate) insults. We observed that urocortin is 10-fold more potent than CRH in protecting hippocampal neurons from insult, whereas urocortin II is ineffective. RT-PCR and sequencing analyses revealed the presence of both CRHR1 and CRHR2 in the hippocampal cultures, with CRHR1 being expressed at much higher levels than CRHR2. Using subtype-selective CRH receptor antagonists, we provide evidence that the neuroprotective effect of exogenously added urocortin is mediated by CRHR1. Furthermore, we provide evidence that the signaling pathway that mediates the neuroprotective effect of urocortin involves cAMP-dependent protein kinase, protein kinase C, and mitogen-activated protein kinase. This is the first demonstration of a biological activity of urocortin in hippocampal neurons, suggesting a role for the peptide in adaptive responses of hippocampal neurons to potentially lethal oxidative and excitotoxic insults.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
G protein-coupled receptor activity  TAS 70397; 70397 RGD 
G protein-coupled receptor binding  IDA 70397 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Crhr1  (corticotropin releasing hormone receptor 1)
Crhr2  (corticotropin releasing hormone receptor 2)
Ucn  (urocortin)

Objects referenced in this article
Gene Crh corticotropin releasing hormone Rattus norvegicus

Additional Information