Objective: To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na^+-K^+ pump. Methods: Microinjection of respective ...Objective: To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na^+-K^+ pump. Methods: Microinjection of respective heterologous cRNA into the Xenopus oocytes as a model system, and measurement of steady-state currents under two-electrode voltage clamp. Results: The co-expression of the 8-opioid receptor with GAT1, EAAC 1 or the sodium pump resulted in reducing activity of the respective transporter. Opioid receptor activation affected transporter activity in different ways: 1) GAT1 was further inhibited; 2) EAAC1 was stimulated; 3) Na^+-K^+ pump activity interfered with agonist sensitivity of DOR. Pump inhibition led to higher sensitivity for DPDPE. Conclusion: GABA transporter inhibition and glutamate transporter stimulation may counteract pain sensation by affecting the neurotransmitter concentration in the synaptic cleft and, therefore, may contribute synergistically to pain suppression by acupuncture. Sodium pump inhibition by endogenous ouabain may amplify these effects. These synergistic effects may be the molecular mechanism of inhibiting pain sense and/or acupuncture analgesia.展开更多
All plant cells are surrounded by a cell wall that provides cohesion,protection,and a means of directional growth to plants.Cellulose microfibrils contribute the main biomechanical scaffold for most of these walls.The...All plant cells are surrounded by a cell wall that provides cohesion,protection,and a means of directional growth to plants.Cellulose microfibrils contribute the main biomechanical scaffold for most of these walls.The biosynthesis of cellulose,which typically is the most prominent constituent of the cell wall and therefore Earth’s most abundant biopolymer,is finely attuned to developmental and environmental cues.Our understanding of the machinery that catalyzes and regulates cellulose biosynthesis has substantially improved due to recent technological advances in,for example,structural biology and microscopy.Here,we provide a comprehensive overview of the structure,function,and regulation of the cellulose synthesis machinery and its regulatory interactors.We aim to highlight important knowledge gaps in the field,and outline emerging approaches that promise a means to close those gaps.展开更多
基金the Science Foundation of Shanghai Municipal Commission of Science and Technology(05DZ19745,06DZ19732,064319053,07DZ19722,07DZ19733)the National Basic Research Program of China(973 Program,2005CB523306)Shanghai Leading Academic Discipline Project(B112 and T0302)
文摘Objective: To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na^+-K^+ pump. Methods: Microinjection of respective heterologous cRNA into the Xenopus oocytes as a model system, and measurement of steady-state currents under two-electrode voltage clamp. Results: The co-expression of the 8-opioid receptor with GAT1, EAAC 1 or the sodium pump resulted in reducing activity of the respective transporter. Opioid receptor activation affected transporter activity in different ways: 1) GAT1 was further inhibited; 2) EAAC1 was stimulated; 3) Na^+-K^+ pump activity interfered with agonist sensitivity of DOR. Pump inhibition led to higher sensitivity for DPDPE. Conclusion: GABA transporter inhibition and glutamate transporter stimulation may counteract pain sensation by affecting the neurotransmitter concentration in the synaptic cleft and, therefore, may contribute synergistically to pain suppression by acupuncture. Sodium pump inhibition by endogenous ouabain may amplify these effects. These synergistic effects may be the molecular mechanism of inhibiting pain sense and/or acupuncture analgesia.
基金L.B.:EMBO postdoctoral fellowship ALTF 37-2022.S.P.acknowledges the financial aid of Villum Investigator(project ID:25915)DNRF Chair(DNRF155)+6 种基金Novo Nordisk L aureate(NNF190C0056076)Novo Nor-disk Emerging Investigator(NNF200C0060564)Novo Nordisk Data Sci-ence(NNF0068884)Lundbeck Foundation(experiment grant,R346-2020-1546)grantsK.E.H.F.:Novo Nordisk Foundation Industrial Biotechnology and Environmental Biotechnology Postdoctoral grant(NNF210C0071799)Villum Foundation Experiment grant (MIL50427)L.C.N.:EMBO postdoctoral fellowship ALTF 629-2021.
文摘All plant cells are surrounded by a cell wall that provides cohesion,protection,and a means of directional growth to plants.Cellulose microfibrils contribute the main biomechanical scaffold for most of these walls.The biosynthesis of cellulose,which typically is the most prominent constituent of the cell wall and therefore Earth’s most abundant biopolymer,is finely attuned to developmental and environmental cues.Our understanding of the machinery that catalyzes and regulates cellulose biosynthesis has substantially improved due to recent technological advances in,for example,structural biology and microscopy.Here,we provide a comprehensive overview of the structure,function,and regulation of the cellulose synthesis machinery and its regulatory interactors.We aim to highlight important knowledge gaps in the field,and outline emerging approaches that promise a means to close those gaps.