Bertrand Paul P, Hu Xiaoya, Mach John, Bertrand Rebecca L
Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Am J Physiol Gastrointest Liver Physiol. 2008 Dec;295(6):G1228-36. doi: 10.1152/ajpgi.90375.2008. Epub 2008 Oct 16.
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 microM, which decayed to 7 +/- 4 microM. Blockade of SERT with fluoxetine (1 microM) increased the peak compression-evoked release to 19 +/- 9 microM, and the background levels of 5-HT increased to 11 +/- 7 microM (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.
血清素（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。尽管5-HT的释放已有充分记载，但血清素再摄取转运体（SERT）对肠道中5-HT水平及作用的贡献尚不清楚。本研究旨在证明回肠黏膜中SERT的实时活性，并评估使用氟西汀抑制SERT的效果。使用碳纤维电极测量5-HT氧化电流，用力传感器记录环形肌（CM）张力，对大鼠回肠全层制剂的黏膜进行电化学记录。对黏膜施压刺激5-HT峰值释放达12±6微摩尔，随后衰减至7±4微摩尔。用氟西汀（1微摩尔）阻断SERT可使施压诱发的峰值释放增加至19±9微摩尔，5-HT的背景水平增至11±7微摩尔（P<0.05，n=7）。当向黏膜外源性施加5-HT时，氟西汀使氧化电流衰减至50%和80%的时间显著延长。氟西汀还增加了CM的自发运动性（P<0.05；n=7），但未增加CM收缩诱发的5-HT释放（P>0.05，n=5）。总之，这是首次对5-HT在大鼠肠道中的实时摄取进行表征。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。
