Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum

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 α,β‐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.