Plasma serotonin levels and the platelet serotonin transporter
Plasma serotonin levels and the platelet serotonin transporter
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DOI：
10.1111/j.1471-4159.2007.04542.x
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发表时间：
2007-07-01
影响因子：
4.7
通讯作者：
Kilic, F.
中科院分区：
文献类型：
--
作者：
Brenner, B.;Harney, J. T.;Kilic, F.
5-羟色胺（5-HT）是一种血小板储存的血管收缩剂。循环5 HT浓度的改变与包括高血压在内的几种病理状况有关。5-HT的作用由不同类型的受体介导，并由单一的5-HT转运体（SERT）终止。因此，SERT是调节血浆5 HT水平以防止血管收缩从而确保稳定血流的主要机制。在这项研究中，血小板SERT对血浆5 HT水平的反应在两个模型中进行了检查：（i）在患有慢性高血压或血压正常的受试者中;（ii）在从血压正常的受试者中分离并用不同浓度的5 HT预处理的血小板上。在高血压期间，由于V-max的降低（K-m相似），血小板5 HT摄取率较低;此外，V-max的降低主要是由于血小板膜上SERT密度的降低，而全细胞表达无变化。血小板5 HT含量降低33%，血浆5 HT含量升高33%。此外，外源性5-HT通过改变质膜上SERT分子的密度以双相方式改变5-HT摄取速率。因此，我们假设在高血压状态下，血浆5 HT水平升高通过降低质膜上SERT分子的密度诱导血小板中5 HT摄取功能的丧失。通过该机制的反馈效应，血浆5 HT通过调节血小板SERT的摄取特性来控制其自身的浓度水平。
Serotonin (5HT) is a platelet-stored vasoconstrictor. Altered concentrations of circulating 5HT are implicated in several pathologic conditions, including hypertension. The actions of 5HT are mediated by different types of receptors and terminated by a single 5HT transporter (SERT). Therefore, SERT is a major mechanism that regulates plasma 5HT levels to prevent vasoconstriction and thereby secure a stable blood flow. In this study, the response of platelet SERT to the plasma 5HT levels was examined within two models: (i) in subjects with chronic hypertension or normotension; (ii) on platelets isolated from normotensive subjects and pretreated with 5HT at various concentrations. The platelet 5HT uptake rates were lower during hypertension due to a decrease in V-max with a similar K-m; also, the decrease in V-max was primarily due to a decrease in the density of SERT on the platelet membrane, with no change in whole cell expression. Additionally, while the platelet 5HT content decreased 33%, the plasma 5HT content increased 33%. Furthermore, exogenous 5HT altered the 5HT uptake rates by changing the density of SERT molecules on the plasma membrane in a biphasic manner. Therefore, we hypothesize that in a hypertensive state, the elevated plasma 5HT levels induces a loss in 5HT uptake function in platelets via a decrease in the density of SERT molecules on the plasma membrane. Through the feedback effect of this proposed mechanism, plasma 5HT controls its own concentration levels by modulating the uptake properties of platelet SERT.