Serotonin (5-HT) release and uptake measured by real-time electrochemical techniques in the rat ileum
Serotonin (5-HT) release and uptake measured by real-time electrochemical techniques in the rat ileum
复制标题
DOI：
10.1152/ajpgi.90375.2008
复制
发表时间：
2008-12-01
影响因子：
4.5
通讯作者：
Bertrand, Rebecca L.
中科院分区：
文献类型：
--
作者：
Bertrand, Paul P.;Hu, Xiaoya;Bertrand, Rebecca L.
5-羟色胺（5-HT）由肠嗜铬细胞释放，在调节肠道功能中起重要作用。虽然5-HT的释放是有据可查的，但5-羟色胺再摄取转运蛋白（SERT）对肠道中5-HT的水平和作用的贡献尚不清楚。本研究旨在证明回肠粘膜中的实时SERT活性，并评估使用氟西汀抑制SERT的效果。电化学记录从粘膜在全层制备的大鼠回肠使用碳纤维电极测量5-HT氧化电流和力传感器记录环行肌（CM）的张力。粘膜的压缩刺激峰值5-HT释放12 +/- 6 μ M，其衰减至7 +/- 4 μ M。用氟西汀（1 μ M）阻断SERT使峰值压迫诱发的释放增加到19 +/-9 μ M，5-HT的背景水平增加到11 +/-7 μ M（P < 0.05，n = 7）。当5-HT外源性应用于粘膜时，氟西汀导致氧化电流衰减50%和80%的时间显著增加。氟西汀还增加CM自发运动（P < 0.05; n = 7），但不增加CM收缩诱发的5-HT释放（P < 0.05，n = 5）。总之，这是第一次表征的实时摄取5-HT进入大鼠肠道。这些数据表明，SERT在调节到达肠道5-HT受体的5-HT浓度中起重要作用。
Serotonin (5-HT) is released from the enterochromaffin cells and plays an important role in regulating intestinal function. Although the release of 5-HT is well documented, the contribution of the serotonin reuptake transporter (SERT) to the levels and actions of 5-HT in the intestine is unclear. This study aimed to demonstrate real-time SERT activity in ileal mucosa and to assess the effects of SERT inhibition using fluoxetine. Electrochemical recordings were made from the mucosa in full-thickness preparations of rat ileum using a carbon fiber electrode to measure 5-HT oxidation current and a force transducer to record circular muscle (CM) tension. Compression of the mucosa stimulated a peak 5-HT release of 12 +/- 6 mu M, which decayed to 7 +/- 4 mu M. Blockade of SERT with fluoxetine (1 mu M) increased the peak compression-evoked release to 19 +/- 9 mu M, and the background levels of 5-HT increased to 11 +/- 7 mu M (P < 0.05, n = 7). When 5-HT was exogenously applied to the mucosa, fluoxetine caused a significant increase in the time to 50% and 80% decay of the oxidation current. Fluoxetine also increased the spontaneous CM motility (P < 0.05; n = 7) but did not increase the CM contraction-evoked 5-HT release (P < 0.05, n = 5). In conclusion, this is the first characterization of the real-time uptake of 5-HT into the rat intestine. These data suggest that SERT plays an important role in the modulation of 5-HT concentrations that reach intestinal 5-HT receptors.