Heterodimerization of ORL1 and opioid receptors and its consequences for N-type calcium channel regulation

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dc.contributor.authorYou, Haitao
dc.contributor.authorHameed, Shahid
dc.contributor.authorAltier, Christophe
dc.contributor.authorMezghrani, Alexandre
dc.contributor.authorBourinet, Emmanuel
dc.contributor.authorEvans, Rhian M.
dc.contributor.authorZamponi, Gerald W.
dc.date.accessioned2018-05-28T17:20:30Z
dc.date.available2018-05-28T17:20:30Z
dc.date.issued2010-01-08
dc.description.abstractWe have investigated the heterodimerization of ORL1 receptors and classical members of the opioid receptor family. All three classes of opioid receptors could be co-immunoprecipitated with ORL1 receptors from both transfected tsA-201 cell lysate and rat dorsal root ganglia lysate, suggesting that these receptors can form heterodimers. Consistent with this hypothesis, in cells expressing either one of the opioid receptors together with ORL1, prolonged ORL1 receptor activation via nociceptin application resulted in internalization of the opioid receptors. Conversely, mu-, delta-, and kappa-opioid receptor activation with the appropriate ligands triggered the internalization of ORL1. The mu-opioid receptor/ORL1 receptor heterodimers were shown to associate with N-type calcium channels, with activation of mu-opioid receptors triggering N-type channel internalization, but only in the presence of ORL1. Furthermore, the formation of opioid receptor/ORL1 receptor heterodimers attenuated the ORL1 receptor-mediated inhibition of N-type channels, in part because of constitutive opioid receptor activity. Collectively, our data support the existence of heterodimers between ORL1 and classical opioid receptors, with profound implications for effectors such as N-type calcium channels.en_US
dc.identifier.citationEvans, R. M., You, H., Hameed, S., Altier, C., Mezghrani, A., Bourinet, E., & Zamponi, G. W. (2010). Heterodimerization of ORL1 and opioid receptors and its consequences for N-type calcium channel regulation. Journal of Biological Chemistry, 285(2), 1032–1040. https://doi.org/10.1074/jbc.M109.040634en_US
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M109.040634en_US
dc.identifier.urihttp://hdl.handle.net/1880/106692
dc.language.isoenen_US
dc.publisherThe American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.publisher.departmentPhysiology & Pharmacologyen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleHeterodimerization of ORL1 and opioid receptors and its consequences for N-type calcium channel regulationen_US
dc.typeunknown
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