Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation.
Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation.
复制标题
肺部血清素吸收模型显示内皮转运蛋白在裂隙渗透中占主导地位。
DOI：
10.1152/ajplung.00420.2012
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Bassingthwaighte,JamesB
中科院分区：
文献类型：
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作者：
Jardine,Bartholomew;Bassingthwaighte,JamesB
四区域（毛细血管血浆、内皮、间质液、细胞）多路径模型被配置为描述肺中小溶质的血液-组织交换动力学，解释区域流动异质性、细胞膜渗透和通过内皮间裂隙以及细胞内反应。来自Rickaby及其同事的多指示剂稀释“推注扫描”实验的血清素摄取数据（Rickaby DA，Linehan JH，Bronikowski TA，Dawson CA.J Appl Physiol 51：405-414，1981; Rickaby DA，Dawson CA和Linehan JH.J Appl Physiol 56：1170-1177，1984）和Malcorp et al.（Malcorps CM，Dawson CA，Linehan JH，Bronikowski TA，Rickaby DA，赫尔曼AG，Will JA.应用生理学杂志57：720-730，1984）进行分析，以区分促进转运进入内皮细胞（EC）和注射物团中非示踪剂5-羟色胺对示踪剂转运的抑制与通过裂隙进入间质液空间的自由未受抑制的渗透。5-羟色胺通过EC间裂隙的渗透性-表面积乘积（PS）为1.03 ml·g−1·min−1，低于转运蛋白介导的最大PS 13 ml·g−1·min−1（Km = 1.03 μM，Vmax = 1.44 nmol·g−1·min−1）。从他们的多个数据集的EC转运蛋白的血清素PS值的估计是相似的，并只受到轻微的影响，占平行的裂缝渗透性。在这些林格氏灌注肺中的裂PS估计值不到麻醉犬的一半（Yipintellectual T.Circ Res 39：523-531，1976），但与后来在同一实验室中观察到的被动非载体介导转运相容（Dawson CA，Linehan JH，Rickaby DA，Bronikowski TA.Ann Biomed Eng 15：217-227，1987; Peeters FAM，Bronikowski TA，Dawson CA，Linehan JH，Bult H，赫尔曼AG.应用生理学杂志66：2328-2337，1989）从这些研究中鉴定和定量裂缝途径传导性证实了裂缝渗透的重要性。
A four-region (capillary plasma, endothelium, interstitial fluid, cell) multipath model was configured to describe the kinetics of blood-tissue exchange for small solutes in the lung, accounting for regional flow heterogeneity, permeation of cell membranes and through interendothelial clefts, and intracellular reactions. Serotonin uptake data from the Multiple indicator dilution “bolus sweep” experiments of Rickaby and coworkers (Rickaby DA, Linehan JH, Bronikowski TA, Dawson CA.J Appl Physiol51: 405–414, 1981; Rickaby DA, Dawson CA, and Linehan JH.J Appl Physiol56: 1170–1177, 1984) and Malcorps et al. (Malcorps CM, Dawson CA, Linehan JH, Bronikowski TA, Rickaby DA, Herman AG, Will JA.J Appl Physiol57: 720–730, 1984) were analyzed to distinguish facilitated transport into the endothelial cells (EC) and the inhibition of tracer transport by nontracer serotonin in the bolus of injectate from the free uninhibited permeation through the clefts into the interstitial fluid space. The permeability-surface area products (PS) for serotonin via the inter-EC clefts were ∼0.3 ml·g−1·min−1, low compared with the transporter-mediated maximum PS of 13 ml·g−1·min−1(withKm= ∼0.3 μM andVmax= ∼4 nmol·g−1·min−1). The estimates of serotonin PS values for EC transporters from their multiple data sets were similar and were influenced only modestly by accounting for the cleft permeability in parallel. The cleft PS estimates in these Ringer-perfused lungs are less than half of those for anesthetized dogs (Yipintsoi T.Circ Res39: 523–531, 1976) with normal hematocrits, but are compatible with passive noncarrier-mediated transport observed later in the same laboratory (Dawson CA, Linehan JH, Rickaby DA, Bronikowski TA.Ann Biomed Eng15: 217–227, 1987; Peeters FAM, Bronikowski TA, Dawson CA, Linehan JH, Bult H, Herman AG.J Appl Physiol66: 2328–2337, 1989) The identification and quantitation of the cleft pathway conductance from these studies affirms the importance of the cleft permeation.