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Title

Upregulation of IRAS/nischarin (I1-imidazoline receptor), a regulatory protein of μ-opioid receptor trafficking, in postmortem prefrontal cortex of long-term opiate and mixed opiate/cocaine abusers

Authors
García-Sevilla, Jesús A
Published in Neurochemistry International. 2017, vol. 108, p. 282-286
Abstract Imidazoline receptor antisera-selected (IRAS)/nischarin, a putative I1-imidazoline receptor, has recently been shown to regulate μ-opioid receptor (OR) trafficking and resensitisation. To study a possible involvement of this μ-OR regulator in opiate dependence, the present study assessed by Western blot analysis the contents of IRAS/nischarin and μ-OR in total homogenates and subcellular preparations of postmortem human prefrontal cortex (PFC/BA9) of long-term opiate and mixed opiate/cocaine abusers as well as of matched healthy control subjects. In the PFC/BA9 of long-term opiate/cocaine abusers (all subjects together) IRAS/nischarin content was increased (+67%, p < 0.01, n = 11) when compared with matched controls (n = 10). Similar increases were found for the subgroups of opiate (+72%, n = 6) and mixed opiate/cocaine (+61%, n = 5) abusers. IRAS/nischarin immunocontents were also found increased in subcellular membrane preparations (+61%, p < 0.05, n = 10) of PFC/BA9 from opiate addicts. In the same brain samples, the levels of μ-OR were not different to those in control subjects. Based on the increased contents in brains of opiate abusers and the reported function as μ-OR regulator, IRAS/nischarin could represent a new promising target for treatment of opiate use disorder.
Keywords AdultCocaine-Related Disorders/metabolism/pathologyFemaleHumansImidazoline Receptors/biosynthesisIntracellular Signaling Peptides and Proteins/biosynthesisMaleMiddle AgedOpioid-Related Disorders/metabolism/pathologyPrefrontal Cortex/metabolism/pathologyProtein Transport/physiologyReceptorsOpioidMu/metabolismTime FactorsUp-Regulation/physiologyIRAS/nischarinΜ-Opioid receptorOpiate dependenceImidazoline receptors
Identifiers
PMID: 28461172
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Research group Groupe Silke Grabherr (969)
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KELLER, Benjamin, LA HARPE, Romano, GARCÍA-SEVILLA, Jesús A. Upregulation of IRAS/nischarin (I1-imidazoline receptor), a regulatory protein of μ-opioid receptor trafficking, in postmortem prefrontal cortex of long-term opiate and mixed opiate/cocaine abusers. In: Neurochemistry International, 2017, vol. 108, p. 282-286. doi: 10.1016/j.neuint.2017.04.017 https://archive-ouverte.unige.ch/unige:125929

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Deposited on : 2019-11-12

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