Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum
Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum
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DOI：
10.1211/jpp.58.2.0006
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发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Takahashi, K
中科院分区：
文献类型：
--
作者：
Kinoshita, N;Takahashi, T;Takahashi, K
虽然目前还没有关于细胞外核苷酸对肠道药物吸收影响的报道，但众所周知，细胞外核苷酸是肠上皮离子运输的重要调节因子。本报告以异硫氰酸荧光素葡聚糖4000 （FD-4）为模型化合物，首次研究了嘌呤核苷酸对肠道吸收不良药物的影响。ATP以浓度依赖性的方式促进FD-4在大鼠回肠的吸收。ADP还增强了FD-4的吸收。其他嘌呤核苷酸（腺苷、AMP、UTP和UDP）没有增强吸收的作用。P2受体拮抗剂苏拉明和吡啶多磷酸-6-偶氮苯基-2′，4′-二磺酸盐（PPADS）可抑制ATP的吸收增强作用。此外，2-甲基硫代ATP（一种P2Y受体激动剂）增强了FD-4的吸收，但α， β -亚甲基ATP（一种P2X受体激动剂）没有。这些发现表明，激活P2Y受体可能会改善回肠对水溶性和高分子化合物的吸收。
While there are no reports concerning the effects of extracellular nucleotides on the intestinal absorption of drugs, it is well known that extracellular nucleotides are important regulators of intestinal epithelial ion transport. This report using fluorescein isothiocyanate dextran 4000 (FD-4) as the model compound is the first to investigate the effects of purine nucleotides on absorption of poorly absorbed drugs from intestine. ATP enhanced the absorption of FD-4 from rat ileum in a concentration-dependent manner. ADP also enhanced the absorption of FD-4. Other purine nucleotides (adenosine, AMP, UTP and UDP) did not show an absorption-enhancing effect. The absorption-enhancing effect by ATP was inhibited by suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS), which are known P2 receptor antagonists. Additionally, 2-methylthio ATP (a P2Y receptor agonist) enhanced the absorption of FD-4, but alpha,beta-methylene ATP (a P2X receptor agonist) did not. These findings suggest that activation of the P2Y receptor may improve the absorption of water-soluble and high-molecular compounds from the ileum.