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Title: Activation of μ-opioid receptor and Toll-like receptor 4 by plasma from morphine-treated mice
Authors: Xie, N
Gomes, FP
Deora, V
Gregory, K
Vithanage, T
Nassar, ZD
Cabot, PJ
Sturgess, P
Shaw, PN
Parat, MO
Keywords: morphine
μ-Opioid receptor
Issue Date: Mar-2017
Source: Xie N, Gomes FP, Deora V, Gregory K, Vithanage T, Nassar ZD, Cabot PJ, Sturgess D, Shaw PN, Parat M-O. Activation of m-opioid receptor and Toll-like receptor 4 by plasma from morphine-treated mice. Brain, Behav. Immun. 2017;61:244-258.
Abstract: In this study, we quantified the ability of opioids present in biological samples to activate the μ-opioid receptor and TLR4 using cell-based assays. Each assay was standardised, in the presence of plasma, using morphine, its μ receptor-active metabolite morphine-6 glucuronide (M6G) and its μ receptor-inactive, but TLR4-active metabolite morphine-3 glucuronide (M3G). Specificity was verified using antagonists. Morphine- and M6G-spiked plasma samples exhibited μ receptor activation, which M3G-spiked plasma lacked. In contrast, M3G showed moderate but consistent activation of TLR-4. Plasma samples were collected at a number of time points from mice administered morphine (1 or 10mg/kg every 12h for 3days) or saline. Morphine administration led to intermittent μ receptor activation, reversed by μ receptor antagonists, and to TRL4 activation at time points where M3G is measured in plasma. Interestingly, this protocol of morphine administration also led to TLR4-independent NF-κB activation, at time points where M3G was not detected, presumably via elevation of circulating cytokines including, but not limited to, TNFα. Circulating TNFα was increased after three days of morphine administration, and TNFα mRNA elevated in the spleen of morphine-treated mice.
Description: Acknowledgement: This study was supported in part by the Anaesthesia and Pain Medicine Foundation, Australian and New Zealand College of Anaesthetists (Project Grant 14/020).
DOI: 10.1016/j.bbi.2016.12.002
PubMed URL:
ISSN: 0889-1591
Journal Title: Brain, behavior, and immunity
Type: Journal Article
Affiliates: Australian and New Zealand College of Anaesthetists
Appears in Collections:Scholarly and Clinical

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