Activation of μ-opioid receptor and Toll-like receptor 4 by plasma from morphine-treated mice
Autor: | Fabio Pereira Gomes, Peter J. Cabot, Kye Gregory, Vandana Deora, Nan Xie, Paul N. Shaw, Tharindu Vithanage, Zeyad D. Nassar, Marie-Odile Parat, David Sturgess |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.drug_class Metabolite Immunology Receptors Opioid mu Spleen Pharmacology 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Mice Plasma Opioid receptor medicine Animals Humans Receptor Morphine Derivatives Morphine Endocrine and Autonomic Systems Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure HEK293 Cells chemistry TLR4 Tumor necrosis factor alpha Female Glucuronide medicine.drug Signal Transduction |
Zdroj: | Brain, behavior, and immunity. 61 |
ISSN: | 1090-2139 |
Popis: | 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 10 mg/kg every 12 h for 3 days) 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. |
Databáze: | OpenAIRE |
Externí odkaz: |