Effect of neurohumoral control on gastrointestinal absorption of drugs

神经体液控制对药物胃肠道吸收的影响

• 批准号: 09672229
• 负责人: OGAWARA Ken-ichi
• 金额: $ 2.05万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672229/
• 关键词: enteric nervous system; adrenergic neuron; cholinergic neuron; epinephrine; bethanechol; myenteric plexus; Enteric nervous system; Epinephrine; Bethanechol; Auerbach神経叢; enteric nervous system; 消化管吸収; 単純拡散; 交感神経系; 吸収促進; 吸収抑制; 一酸化窒素; 非アドレナ

In the present study, we tried to investigate the effect of enteric nervous system (ENS) on the drug absorption via passive diffusion mechanism, using phenol red (PR) as a poorly absorbable model compound. To modulate ENS, epinephrine and bethanechol were employed, and their effects were evaluated by the vascular and luminal perfusion study in rat small intestine and the in vitro transport study using the side-by-side diffusion chamber.The infusion of epinephrine increased water absorption. On the contrary, the absorption of PR was significantly reduced by epinephrine and this effect of epinephrine disappeared by removing epinephrine from the vascular perfusate, indicating that the effects of epinephrine should be reversible, In the diffusion chamber experiments using rat jejunum, epinephrine rapidly reduced initial PD and Isc, which would be ascribed to the enhancement of chloride absorption. Rm and the absorption of PR increased and reduced with the addition of epinephrine, respectively. These results suggest that adrenergic nerves might regulate the passive transport of drugs by modulating tight junction, but not by solvent drag.The addition of bethanechol into vascular perfusate converted net water flux to secretion during both the drug infusion and recovery periods, At the beginning of bethanechol infusion, the absorption rate of PR slightly decreased, and then PR absorption increased. Removing bethanechol from the vascular perfusate rapidly reduced the absorption of PR.From these results, it was found that ENS should regulate not only the blood flow, the intestinal motility and the transport of water and/or electrolytes but also the absorption of drug in the intestine.

本研究以酚红（PR）为吸收不良模型化合物，通过被动扩散机制探讨肠神经系统（ENS）对药物吸收的影响。通过大鼠小肠血管灌流和小肠腔灌流研究以及体外扩散室研究，观察了肾上腺素和氨甲酰胆碱对ENS的调节作用。相反，肾上腺素显著降低PR的吸收，并且从血管灌注液中去除肾上腺素后，肾上腺素的这种作用消失，表明肾上腺素的作用应该是可逆的。在大鼠空肠扩散室实验中，肾上腺素迅速降低初始PD和Isc，这归因于增强氯离子吸收。加入肾上腺素后，RM增加，PR吸收减少。结果表明，肾上腺素能神经可能通过调节紧密连接而不是通过溶剂阻力来调节药物的被动转运，在药物灌注期和恢复期，向血管灌流液中加入氨甲酰甲胆碱可使净水通量转化为分泌，在氨甲酰甲胆碱灌注初期，PR的吸收率略有下降，随后PR的吸收率增加。从血管灌流液中去除氨甲酰胆碱迅速降低PR的吸收。从这些结果中发现，ENS不仅应调节血流量，肠蠕动和水和/或电解质的运输，而且还应调节药物在肠道中的吸收。