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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
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: |
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| 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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