Cellular Signaling Mechanisms of Hypocretin/Orexin

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Kukkonen , J P & Turunen , P M 2021 , ' Cellular Signaling Mechanisms of Hypocretin/Orexin ' , Frontiers of Neurology and Neuroscience , vol. 45 , pp. 91-102 . https://doi.org/10.1159/000514962

Title: Cellular Signaling Mechanisms of Hypocretin/Orexin
Author: Kukkonen, Jyrki P.; Turunen, Pauli M.
Contributor organization: Department of Pharmacology
Department of Physiology
Date: 2021
Language: eng
Number of pages: 12
Belongs to series: Frontiers of Neurology and Neuroscience
ISSN: 1660-4431
DOI: https://doi.org/10.1159/000514962
URI: http://hdl.handle.net/10138/341165
Abstract: Orexin receptors (OXRs) are promiscuous G-protein-coupled receptors that signal via several G-proteins and, putatively, via other proteins. On which basis the signal pathways are selected and orchestrated is largely unknown. We also have an insufficient understanding of the kind of signaling that is important for specific types of cellular responses. OXRs are able to form complexes with several other G-protein-coupled receptors in vitro, and one possibility is that the complexing partners regulate the use of certain signal transducers. In the central nervous system neurons, the main acute downstream responses of OXR activation are the inhibition of K+ channels and the activation of the Na+/Ca2+ exchanger and non-selective cation channels of unknown identity. The exact nature of the intracellular signal chain between the OXRs and these downstream targets is yet to be elucidated, but the Gq-phospholipase C (PLC) protein kinase C pathway - which is a significant signaling pathway for OXRs in recombinant cells - may be one of the players in neurons. The Gq-PLC pathway may also, under certain circumstances, take the route to diacylglycerol lipase, which leads to the production of the potent endocannabinoid (eCB), 2-arachidonoyl glycerol, and thereby connects orexins with eCB signaling. In addition, OXRs have been studied in the context of neurodegeneration and cancer cell death. Overall, OXR signaling is complex, and it can change depending on the cell type and environment.
Description: Publisher Copyright: © 2021 The Author(s).
Subject: 3111 Biomedicine
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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