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Insights into mechanisms of corticotropin-releasing hormone receptor signal transduction

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Grammatopoulos, Dimitris (2012) Insights into mechanisms of corticotropin-releasing hormone receptor signal transduction. British Journal of Pharmacology, Vol.166 (No.1). pp. 85-97. doi:10.1111/j.1476-5381.2011.01631.x

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Official URL: http://dx.doi.org/10.1111/j.1476-5381.2011.01631.x

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Abstract

During evolution, mammals have developed remarkably similar molecular mechanisms to respond to external challenges and maintain survival. Critical regulators of these mechanisms are the family of ‘stress’-peptides that consists of the corticotropin-releasing hormone (CRH) and urocortins (Ucns). These neuropeptides ‘fine-tune’ integration of an intricate series of physiological responses involving the autonomic, endocrine, immune, cardiovascular and reproductive systems, which
induce a spectrum of behavioural and homeostatic changes. CRH and Ucns exert their actions by activating two types of CRH receptors (CRH-R), CRH-R1 and CRH-R2, which belong to the class-B1 family of GPCRs. The CRH-Rs exhibit signalling promiscuity facilitated by their ability to couple to multiple G-proteins and regulate diverse intracellular networks that involve intracellular effectors such as cAMP and an array of PKs in an agonist and tissue-specific manner, a property that allows them
to exert unique roles in the integration of homeostatic mechanisms. We only now begin to unravel the plethora of CRH-R biological actions and the transcriptional and post-translational mechanisms such as alternative mRNA splicing or phosphorylation-mediated desensitization developed to tightly control CRH-Rs biological activity and regulate their physiological actions. This review summarizes the current understanding of CRH-R signalling complexity and regulatory mechanisms that underpin cellular responses to CRH and Ucn

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School
Journal or Publication Title: British Journal of Pharmacology
Publisher: John Wiley & Sons Ltd.
ISSN: 1476-5381
Official Date: 2012
Dates:
DateEvent
2012Published
Volume: Vol.166
Number: No.1
Page Range: pp. 85-97
DOI: 10.1111/j.1476-5381.2011.01631.x
Status: Peer Reviewed
Publication Status: Published

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