Deletion of Crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2
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- 1 April 2000
- journal article
- Published by Springer Nature in Nature Genetics
- Vol. 24 (4) , 415-419
- https://doi.org/10.1038/74271
Abstract
Corticotropin-releasing hormone (Crh), a 41-residue polypeptide, activates two G-protein-coupled receptors, Crhr1 and Crhr2, causing (among other transductional events) phosphorylation of the transcription factor Creb. The physiologic role of these receptors is only partially understood. Here we report that male, but not female, Crhr2-deficient mice exhibit enhanced anxious behaviour in several tests of anxiety in contrast to mice lacking Crhr1. The enhanced anxiety of Crhr2-deficient mice is not due to changes in hypothalamic-pituitary-adrenal (HPA) axis activity, but rather reflects impaired responses in specific brain regions involved in emotional and autonomic function, as monitored by a reduction of Creb phosphorylation in male, but not female, Crhr2-/- mice. We propose that Crhr2 predominantly mediates a central anxiolytic response, opposing the general anxiogenic effect of Crh mediated by Crhr1. Neither male nor female Crhr2-deficient mice show alterations of baseline feeding behaviour. Both respond with increased edema formation in response to thermal exposure, however, indicating that in contrast to its central role in anxiety, the peripheral role of Crhr2 in vascular permeability is independent of gender.Keywords
This publication has 27 references indexed in Scilit:
- Corticotropin-Releasing Factor Type 1 and Type 2α Receptors Regulate Phosphorylation of Calcium/Cyclic Adenosine 3′,5′-Monophosphate Response Element-Binding Protein and Activation of p42/p44 Mitogen-Activated Protein KinaseEndocrinology, 1999
- Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1Nature Genetics, 1998
- Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart.Proceedings of the National Academy of Sciences, 1995
- A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle.Proceedings of the National Academy of Sciences, 1995
- Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain.Proceedings of the National Academy of Sciences, 1995
- Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brainNeuron, 1993
- Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptorsFEBS Letters, 1993
- Expression cloning of a human corticotropin-releasing-factor receptor.Proceedings of the National Academy of Sciences, 1993
- Primary structure of corticotropin-releasing factor from ovine hypothalamus.Proceedings of the National Academy of Sciences, 1981
- Characterization of a 41-Residue Ovine Hypothalamic Peptide That Stimulates Secretion of Corticotropin and β-EndorphinScience, 1981