Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor ...Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.展开更多
基金supported by the Russian Science Foundation(Grant No.23-65-10017 to B.K.K.and M.K.)The Ministry of Science and Higher Education of the Russian Federation(Grant No.122020300042-4 to L.N.M.)supported the preparation of the minichapter titled"Opioids reduce inflammatory injury of the heart".
文摘Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.
