Chen J J, Li Z, Pan H, Murphy D L, Tamir H, Koepsell H, Gershon M D
Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
J Neurosci. 2001 Aug 15;21(16):6348-61. doi: 10.1523/JNEUROSCI.21-16-06348.2001.
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.
肠5-羟色胺再摄取转运体（SERT）被认为在5-羟色胺能神经传递以及蠕动和分泌反射的起始过程中发挥关键作用。我们分析了SERT靶向缺失小鼠肠道中的潜在代偿机制和肠道功能。发现这些动物的肠道缺乏编码SERT的mRNA；此外，5-羟色胺（5-HT）向SERT +/+ 小鼠肠道上皮细胞、肥大细胞和肠神经元的高亲和力摄取在SERT -/- 小鼠肠道中不存在。然而，SERT +/+ 小鼠肠道和SERT -/- 小鼠肠道均表达能够转运5-HT的分子，但亲和力和选择性远低于SERT。这些分子包括多巴胺转运体（DAT）以及多特异性有机阳离子转运体OCT-1和OCT-3。DAT和OCT免疫反应性存在于黏膜下神经丛和肌间神经丛中，OCTs也位于黏膜上皮。在SERT -/- 小鼠肠道中，5-HT存在于其所有正常部位，该肠道含有编码色氨酸羟化酶的mRNA，但SERT -/- 动物的血液中不存在5-HT。大多数SERT -/- 动物的粪便含水量和结肠蠕动增加；然而，蠕动增加（腹泻）偶尔会与蠕动减少（便秘）不规则交替。水样腹泻可能归因于SERT -/- 小鼠中5-羟色胺能信号的增强，而短暂性便秘可能是由5-HT释放增加导致5-HT受体脱敏的发作引起的。
