G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,ta...G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all marketed drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respiration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alzheimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.展开更多
目的:通过大样本信息化真实世界研究,评价分析止吐药帕洛诺司琼致心律失常的发生率、临床特征和危险因素,为临床安全用药提供参考。方法:依托临床ADE主动监测与智能评估警示系统-Ⅱ(adverse drug event active surveillance and assessm...目的:通过大样本信息化真实世界研究,评价分析止吐药帕洛诺司琼致心律失常的发生率、临床特征和危险因素,为临床安全用药提供参考。方法:依托临床ADE主动监测与智能评估警示系统-Ⅱ(adverse drug event active surveillance and assessment system-Ⅱ,ADE-ASAS-Ⅱ)对2017年至2021年某院使用该药的住院患者开展回顾性自动监测,获取心律失常发生率和临床特征,通过Logistic回归分析确定危险因素。结果:纳入30445例患者,用药78232例次,最终确定165例次发生心律失常,发生率0.21%。使用该药患者发生心律失常的独立危险因素有合并心血管疾病、天冬氨酸氨基转移酶>40 U·L^(-1)和用药时间延长;此外,使用该药预防化疗后恶心、呕吐患者的独立危险因素还包括肌钙蛋白T>0.13μg·mL^(-1)、氨基末端脑钠肽前体>900 pg·mL^(-1)和联用环磷酰胺,预防术后恶心、呕吐患者的独立危险因素还包括钾<3.5 mmol·L^(-1)、静脉泵入给药、联用其他5-羟色胺3受体拮抗剂(5-hydroxytryptamine 3 receptor antagonists,5-HT3RA)或氟氧头孢。结论:帕洛诺司琼致心律失常与前述危险因素显著相关,发生率属偶见范围;ADE-ASAS-Ⅱ能够高效、精准、低成本获取目标用药人群风险信息。展开更多
基金supported the Fund of Sichuan Provincial Department of Science and Technology(Grant No.:2024YFFK0393)the CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.:2019-I2M-5-004).
文摘G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all marketed drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respiration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alzheimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.
文摘目的:通过大样本信息化真实世界研究,评价分析止吐药帕洛诺司琼致心律失常的发生率、临床特征和危险因素,为临床安全用药提供参考。方法:依托临床ADE主动监测与智能评估警示系统-Ⅱ(adverse drug event active surveillance and assessment system-Ⅱ,ADE-ASAS-Ⅱ)对2017年至2021年某院使用该药的住院患者开展回顾性自动监测,获取心律失常发生率和临床特征,通过Logistic回归分析确定危险因素。结果:纳入30445例患者,用药78232例次,最终确定165例次发生心律失常,发生率0.21%。使用该药患者发生心律失常的独立危险因素有合并心血管疾病、天冬氨酸氨基转移酶>40 U·L^(-1)和用药时间延长;此外,使用该药预防化疗后恶心、呕吐患者的独立危险因素还包括肌钙蛋白T>0.13μg·mL^(-1)、氨基末端脑钠肽前体>900 pg·mL^(-1)和联用环磷酰胺,预防术后恶心、呕吐患者的独立危险因素还包括钾<3.5 mmol·L^(-1)、静脉泵入给药、联用其他5-羟色胺3受体拮抗剂(5-hydroxytryptamine 3 receptor antagonists,5-HT3RA)或氟氧头孢。结论:帕洛诺司琼致心律失常与前述危险因素显著相关,发生率属偶见范围;ADE-ASAS-Ⅱ能够高效、精准、低成本获取目标用药人群风险信息。
