Isoflurane alters the amount of dopamine transporter expressed on the plasma membrane in humans.
Isoflurane alters the amount of dopamine transporter expressed on the plasma membrane in humans.
复制标题
异氟烷改变人类质膜上表达的多巴胺转运蛋白的量。
DOI：
10.1097/00000542-200411000-00012
复制
发表时间：
2004
期刊：
影响因子：
8.8
通讯作者：
Goodman,MarkM
中科院分区：
文献类型：
--
作者：
Votaw,JohnR;Byas-Smith,MichaelG;Voll,Ronald;Halkar,Raghu;Goodman,MarkM
异氟醚增加细胞外多巴胺浓度，导致转染细胞内多巴胺转运蛋白（DAT）的运输。此外，高度特异性的正电子发射DAT配体的结合电位被异氟烷在恒河猴中改变。本研究的目的是确定异氟烷改变这些配体之一（[F-18]FECNT）在humans.MethodsTwenty人类志愿者进行正电子发射断层扫描使用[F-18] FECNT的结合潜力的剂量反应曲线。所有受试者在清醒时进行扫描，然后在分配到四组之一（每组n = 5）后再次进行扫描：清醒控制，丙泊酚控制，或轻度或深度异氟烷麻醉，由脑电双频指数监测定义。轻度麻醉组的脑电双频指数值为40 +/- 7（潮气末异氟烷，1.02 +/- 0.08），而深度麻醉组为27 +/- 10（潮气末异氟烷，1.6 +/- 0.3）。清醒和第二次扫描之间的壳核结合电位的受试者内的百分比变化，确定为每个主题，平均组内，并比较groups.ResultsThe [F-18]FECNT结合电位表现出作为麻醉剂量的函数的双相形状。清醒对照组和丙泊酚对照组第二次扫描的结合电位明显低于初次扫描;对于轻度麻醉组，麻醉期间结合电位显著增加，结论异氟醚可引起[F-18]的剂量依赖性变化，FECNT与DAT的结合潜力与异氟烷一致，导致DAT在质膜和细胞内部之间运输。低于最小肺泡浓度的异氟烷浓度导致DAT从细胞内部运输到质膜，但在较高浓度下不发生净运输。如果异氟烷通过间接途径改变功能性表达的DAT的量，则数据最容易解释。这一现象应该得到更充分的探索，以帮助下一代麻醉剂更具体的机制，并减少不希望的副作用。
BackgroundIsoflurane increases extracellular dopamine concentration and causes trafficking of the dopamine transporter (DAT) in transfected cells. Also, the binding potentials of highly specific positron-emitting DAT ligands are altered by isoflurane in rhesus monkeys. The purpose of this study was to determine the dose-response curve for isoflurane altering the binding potential of one of these ligands ([F-18]FECNT) in humans.MethodsTwenty human volunteers underwent positron emission tomography using [F-18]FECNT. All subjects were scanned while awake and then again after assignment to one of four groups (n = 5 each): awake-control, propofol-control, or light or deep isoflurane anesthesia as defined by Bispectral Index monitoring. Bispectral Index values in the light anesthesia group were 40 +/- 7 (end-tidal isoflurane, 1.02 +/- 0.08) versus 27 +/- 10 (end-tidal isoflurane, 1.6 +/- 0.3) in the deep anesthesia group. The within-subject percent change in putamen binding potential between the awake and second scans was determined for each subject, averaged within groups, and compared across groups.ResultsThe [F-18]FECNT binding potential exhibited a biphasic shape as a function of anesthetic dose. The binding potential for the second scan in the awake-control and propofol-control groups was significantly less than the initial scan; for the light anesthesia group, the binding potential was significantly increased during anesthesia, and no change was detected between the two scans in the deeper anesthesia group.ConclusionIsoflurane causes a dose-dependent change in the [F-18]FECNT binding potential for DAT consistent with isoflurane causing trafficking of the DAT between the plasma membrane and the cell interior. Concentrations of isoflurane below minimum alveolar concentration causes DAT to be trafficked to the plasma membrane from the cell interior, but no net trafficking occurs at higher concentrations. The data are most easily explained if isoflurane alters the amount of functionally expressed DAT through an indirect pathway. This phenomena should be more fully explored to help make the next generation of anesthetics more mechanistically specific and to reduce undesired side effects.