Systematic analysis of ENS-regulation of drug absorption

采用Caco-2细胞单层或大鼠离体肠片，以甘露醇为细胞旁转运标记物，安替比林和非那西丁为跨细胞转运标记物，研究肠神经系统对药物被动扩散吸收的影响。刺激肾上腺素能神经元和胆碱能神经元都不影响这些小分子的粘膜转运。然而，肾上腺素能刺激减少或胆碱能刺激增加FD-40穿过肠粘膜的转运。另一方面，通过腹腔注射5-羟色胺和氯吉林制备5-羟色胺综合征模型大鼠。利用从模型大鼠分离的肠片，观察到P-糖蛋白活性的广泛增加，这至少部分归因于P-糖蛋白表达的显著诱导。

Effect of enteric nervous system on drug absorption via passive diffusion was investigated with Caco-2 cells monolayer or isolated rat intestinal sheet by utilizing mannitol as a marker for transport through paracellular route and antipyrine and phenacetin as a marker for transport through transcellular route. Stimulation of neither adrenergic neuron nor cholinergic neuron affects the mucosal transport of these small molecules. However, adrenergic stimulation decreased or cholinergic stimulation increased the transport of FD-40 across the intestinal mucosa. On the other hand, model rats of serotonin syndrome were prepared by intraperitoneal injection of both serotonin and clorgyline. Utilizing an isolated intestinal sheet from the model rat, the extensive increase in P-glycoprotein activity was observed, which was at least partly attributed to the significant induction of P-glycoprotein expression.