CRHR2 Membrane Protein Introduction

Introduction of CRHR2

CRHR2, encoded by CRHR2 gene, also known as CRF2, is a cell-surface protein. It belongs to G-protein coupled receptor family which has seven transmembrane domains. The extracellular domain of receptor responds to peptide hormones, corticotropin-releasing hormone (CRH) and urocortin (UCN), involved in the regulation of response to stress. Most studies have been designed to investigate the CRHR2 possible role in regulating social behavior response to stress.

Function of CRHR2 Membrane Protein

CRHR2 is a receptor for corticotropin-releasing hormone (CRH) and CRH-related peptides such as urocortin. When the receptors bind to its ligands, it will promote the activation of adenylate cyclase, resulting in an intracellular second messenger cAMP levels which activate protein kinase A (PKA) signaling. The results showed that CRHR2 may play a role in the integration of neuroendocrine, autonomic, and behavioral functions. And the deficiency of CRHR2 in mice may present anxiety-like behavior, hypersensitivity to stress, altered feeding behavior and metabolism, and cardiovascular abnormalities. Moreover, CRHR2 may be associated with the pathogenesis of ischemia/reperfusion-induced enteritis, heart failure, irritable bowel syndrome. And a recent study has been shown that CRHR2 antagonist may be used as a promising therapeutic drug to treat chronic heart failure. In addition, CRHR2 is also involved in the pathological processes of cancer. CRF2-signaling can regulate cellular adhesion of human colon cancer cells. And the CRF2 expression in deep infiltrating endometriotic lesions is significantly higher than in ovarian endometrioma.

Fig.1 Corticotropin-releasing hormone signaling pathway.

Application of CRHR2 Membrane Protein in Literature

1. Morisot N., et al. CRF2 receptor-deficiency eliminates social behaviour deficits and vulnerability induced by cocaine. British Journal of Pharmacology. 2018, 175(9): 1504-1518. PubMed ID: 29406581
   
   

   The study reveals that lacking CRF2 receptor reduces social behaviour deficits and vulnerability induced by cocaine withdrawal. These suggest a new therapeutic target for stimulant use disorders.

2. Ducarouge B., et al. Involvement of CRF2 signaling in enterocyte differentiation. World Journal of Gastroenterology. 2017, 23(28): 5127-5145. PubMed ID: 28811708
   
   

   This research implicates that CRF2 signaling could regulate intestinal epithelial cell (IEC) differentiation. The mechanisms could be associated with the stress-induced epithelial alterations found in inflammatory bowel diseases.

3. Tsuda T., et al. Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction. Journal of Experimental Medicine. 2017, 214(7): 1877-1888. PubMed ID: 28550160
   
   

   The research finds that CRF2 is widely expressed in the cardiomyocytes. In mice, continuous infusion of the CRHR2 agonist, urocortin 2 (Ucn2), could reduce left ventricular ejection fraction and lacking CRHR2 could escape from cardiac dysfunction induced by overpressure. These suggest that CRHR2 agonist is a promising drug for chronic heart failure.

4. Pelissierrota M., et al. A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells. Biochim Biophys Acta. 2017, 1864(7): 1246-1259. PubMed ID: 28432022
   
   

   The study reveals that identifies a new intracellular circuit involving mAchR acting on CRF2-signaling that could mediate colonic mucosal barrier dysfunction and exacerbate mucosal inflammation.

5. Bagosi Z., et al. The effects of CRF and urocortins on the preference for social novelty of mice. Behavioural Brain Research. 2017, 324: 146-154. PubMed ID: 28189757
   
   

   The study implicates that activated CRF1 receptor regulates the preference for social novelty by CRF and UCN 1. While selectively activated CRF2 receptor by UCN2 and UCN3 doesn't participate in the male-female interaction.

CRHR2 Preparation Options

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