RGD Reference Report - Activation of corticotropin-releasing factor receptor 2 mediates the colonic motor coping response to acute stress in rodents. - Rat Genome Database

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Activation of corticotropin-releasing factor receptor 2 mediates the colonic motor coping response to acute stress in rodents.

Authors: Gourcerol, G  Wu, SV  Yuan, PQ  Pham, H  Miampamba, M  Larauche, M  Sanders, P  Amano, T  Mulak, A  Im, E  Pothoulakis, C  Rivier, J  Tache, Y  Million, M 
Citation: Gourcerol G, etal., Gastroenterology. 2011 May;140(5):1586-96.e6. Epub 2011 Jan 26.
RGD ID: 5491003
Pubmed: PMID:21277852   (View Abstract at PubMed)
PMCID: PMC3150547   (View Article at PubMed Central)
DOI: DOI:10.1053/j.gastro.2011.01.039   (Journal Full-text)

BACKGROUND & AIMS: Corticotropin-releasing factor receptor-1 (CRF(1)) mediates the stress-induced colonic motor activity. Less is known about the role of CRF(2) in the colonic response to stress. METHODS: We studied colonic contractile activity in rats and CRF(2)-/-, CRF-overexpressing, and wild-type mice using still manometry; we analyzed defecation induced by acute partial-restraint stress (PRS), and/or intraperitoneal injection of CRF ligands. In rats, we monitored activation of the colonic longitudinal muscle myenteric plexus (LMMP) neurons and localization of CRF(1) and CRF(2) using immunohistochemical and immunoblot analyses. We measured phosphorylation of extracellular signal-regulated kinase 1/2 by CRF ligands in primary cultures of LMMP neurons (PC-LMMPn) and cyclic adenosine monophosphate (cAMP) production in human embryonic kidney-293 cells transfected with CRF(1) and/or CRF(2). RESULTS: In rats, a selective agonist of CRF(2) (urocortin 2) reduced CRF-induced defecation (>50%), colonic contractile activity, and Fos expression in the colonic LMMP. A selective antagonist of CRF(2) (astressin(2)-B) increased these responses. Urocortin 2 reduced PRS-induced colonic contractile activity in wild-type and CRF-overexpressing mice, whereas disruption of CRF(2) increased PRS-induced colonic contractile activity and CRF-induced defecation. CRF(2) colocalized with CRF(1) and neuronal nitric oxide synthase in the rat colon, LMMP, and PC-LMMPn. CRF-induced phosphorylation of extracellular signal-regulated kinase in PC-LMMPn; this was inhibited or increased by a selective antagonist of CRF(1) (NBI35965) or astressin(2)-B, respectively. The half maximal effective concentration, EC(50), for the CRF-induced cAMP response was 8.6 nmol/L in human embryonic kidney-293 cells that express only CRF(1); this response was suppressed 10-fold in cells that express CRF(1) and CRF(2). CONCLUSIONS: In colon tissues of rodents, CRF(2) activation inhibits CRF(1) signaling in myenteric neurons and the stress-induced colonic motor responses. Disruption of CRF(2) function impairs colonic coping responses to stress.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of defecation  IMP 5491003 RGD 
positive regulation of cAMP-mediated signaling  IDA 5491003 RGD 
regulation of ERK1 and ERK2 cascade  IMP 5491003 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell body fiber  IDA 5491003 RGD 
neuronal cell body  IDA 5491003 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Crhr2  (corticotropin releasing hormone receptor 2)

Objects referenced in this article
Gene Crhr1 corticotropin releasing hormone receptor 1 Rattus norvegicus

Additional Information