Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters
Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters
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DOI：
10.1523/jneurosci.21-16-06348.2001
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发表时间：
2001-08-15
影响因子：
5.3
通讯作者：
Gershon, MD
中科院分区：
文献类型：
--
作者：
Chen, JJ;Li, ZS;Gershon, MD
肠道5-羟色胺再摄取转运蛋白（SERT）被认为在多巴胺能神经传递以及蠕动和分泌反射的启动中起关键作用。我们分析了潜在的代偿机制和肠道功能的小鼠肠道有针对性的删除SERT。发现这些动物的肠道缺乏编码SERT的mRNA;此外，在SERT +/+肠中存在5-HT高亲和力摄取到上皮细胞、肥大细胞和肠神经元中，但在SERT -/-肠中不存在。然而，SERT +/+肠和-/-肠都表达能够转运5-HT的分子，但亲和力和选择性远低于SERT。这些包括多巴胺转运蛋白（DAT）和多特异性有机阳离子转运蛋白OCT-1和OCT-3。DAT和OCT的免疫反应存在于粘膜下和肌间神经丛，OCT也位于粘膜上皮。5-HT在SERT -/-肠中的所有正常位点都被发现，其中含有编码色氨酸羟化酶的mRNA，但在SERT -/-动物的血液中不存在5-HT。在大多数SERT -/-动物中，粪便水和结肠运动性增加;然而，运动性增加（腹泻）偶尔与运动性降低（便秘）不规则交替。水样腹泻可能是由于增强SERT -/-小鼠中的多巴胺能信号传导，而短暂性便秘可能是由增强的5-HT释放导致5-HT受体脱敏引起的。
The enteric serotonin reuptake transporter (SERT) has been proposed to play a critical role in serotonergic neurotransmission and in the initiation of peristaltic and secretory reflexes. We analyzed potential compensatory mechanisms and enteric function in the bowels of mice with a targeted deletion of SERT. The guts of these animals were found to lack mRNA encoding SERT; moreover, high-affinity uptake of 5-HT into epithelial cells, mast cells, and enteric neurons was present in the SERT +/+ bowel but absent in the SERT -/- bowel. However, both the SERT +/+ gut and the -/- gut expressed molecules capable of transporting 5-HT, but with affinities and selectivity much lower than those of SERT. These included the dopamine transporter (DAT) and polyspecific organic cation transporters OCT-1 and OCT-3. DAT and OCT immunoreactivities were present in both the submucosal and myenteric plexuses, and the OCTs were also located in the mucosal epithelium. 5-HT was found in all of its normal sites in the SERT -/- bowel, which contained mRNA encoding tryptophan hydroxylase, but no 5-HT was present in the blood of SERT -/- animals. Stool water and colon motility were increased in most SERT -/- animals; however, the increase in motility (diarrhea) occasionally alternated irregularly with decreased motility (constipation). The watery diarrhea is probably attributable to the potentiation of serotonergic signaling in SERT -/- mice, whereas the transient constipation may be caused by episodes of enhanced 5-HT release leading to 5-HT receptor desensitization.