Cannabinoid Agonists Increase the Interaction between β-Arrestin 2 and ERK1/2 and Upregulate β-Arrestin 2 and 5-HT2A Receptors
dc.contributor.author | Franklin, Jade M. | |
dc.contributor.author | Vasiljevik, Tamara | |
dc.contributor.author | Prisinzano, Thomas E. | |
dc.contributor.author | Carrasco, Gonzalo A. | |
dc.date.accessioned | 2017-05-08T20:48:34Z | |
dc.date.available | 2017-05-08T20:48:34Z | |
dc.date.issued | 2012-11-19 | |
dc.identifier.citation | Franklin, Jade M. et al. “Cannabinoid Agonists Increase the Interaction between Β-Arrestin 2 and ERK1/2 and Upregulate Β-Arrestin 2 and 5-HT2A Receptors.” Pharmacological research : the official journal of the Italian Pharmacological Society 68.1 (2013): 46–58. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24032 | |
dc.description.abstract | We have recently reported that selective cannabinoid 2 (CB2) receptor agonists upregulate 5-HT2A receptors by enhancing ERK1/2 signaling in prefrontal cortex (PFCx). Increased activity of cortical 5-HT2A receptors has been associated with several neuropsychiatric disorders such as anxiety and schizophrenia. Here we examine the mechanisms involved in this enhanced ERK1/2 activation in rat PFCx and in a neuronal cell model. Sprague-Dawley rats treated with a non-selective cannabinoid agonist (CP55940, 50 μg/kg, 7 days, i.p.) showed enhanced co-immunoprecipitation of β-Arrestin 2 and ERK1/2, enhanced pERK protein levels, and enhanced expression of β-Arrestin 2 mRNA and protein levels in PFCx. In a neuronal cell line, we found that selective CB2 receptor agonists upregulate β-Arrestin 2, an effect that was prevented by selective CB2 receptor antagonist JTE-907 and CB2 shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis, ERK1/2, and the AP-1 transcription factor also prevented the cannabinoid receptor-induced upregulation of β-Arrestin 2. Our results suggest that sustained activation of CB2 receptors would enhance β-Arrestin 2 expression possibly contributing to its increased interaction with ERK1/2 thereby driving the upregulation of 5-HT2A receptors. The CB2 receptor-mediated upregulation of β-Arrestin 2 would be mediated, at least in part, by an ERK1/2-dependent activation of AP-1. These data could provide the rationale for some of the adverse effects associated with repeated cannabinoid exposure and shed light on some CB2 receptor agonists that could represent an alternative therapeutic because of their minimal effect on serotonergic neurotransmission. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.subject | Cannabinoid receptors | en_US |
dc.subject | 5-HT2A receptor | en_US |
dc.subject | ERK1/2 | en_US |
dc.subject | β-Arrestin 2 | en_US |
dc.subject | Prefrontal cortex | en_US |
dc.title | Cannabinoid Agonists Increase the Interaction between β-Arrestin 2 and ERK1/2 and Upregulate β-Arrestin 2 and 5-HT2A Receptors | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Prisinzano, Thomas E. | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1016/j.phrs.2012.11.002 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3562593 | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.