Analysis of drug absorption behavior in the enteric nervous system-related gastrointestinal diseases

5-羟色胺（5-HT）作为肠神经系统（ENS）的神经递质和胃肠道激素与胃肠道功能调节有关，5-HT代谢紊乱与肠易激综合征等胃肠道疾病有关。在这个项目中，我们评估了5-HT消耗对有机阴离子分泌到小肠腔的影响，影响它们的吸收行为。苯酚红（Phenol red， PR）是一种模型化合物，在Caco-2细胞和大鼠小肠中主要由基侧向根尖转运。此外，基于MRP2和BCRP在5- ht缺失大鼠小肠上皮细胞刷状缘膜中的表达增强，我们发现MRP2和BCRP参与PR的分泌转运，并且在5- ht缺失大鼠中PR的分泌转运显著增强，这是MRP2和BCRP功能增强的原因。

Serotonin (5-HT) is related to the regulation of gastrointestinal (GI) function as a neurotransmitter in enteric nervous system (ENS) and GI hormone, and the disorder of 5-HT metabolism is suggested to associate with several GI diseases such as irritable bowel syndrome. In this project, we evaluated the effect of 5-HT depletion on the secretion of organic anions into the small intestinal lumen, influencing their absorption behavior. Phenol red (PR), a model compound, was clarified to be predominantly transported from basal to apical sides in Caco-2 cells and rat small intestine. Furthermore, it was indicated that MRP2 and BCRP contributed to the secretory transport of PR and that the secretory transport of PR was significantly enhanced in 5-HT-depleted rats, which was responsible for the enhancement of MRP2 and BCRP functions, based on their enhanced expression in the brush border membrane of small intestinal epithelial cells of 5-HT-depleted rats.