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 t...

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Veröffentlicht in:Journal of pharmacy and pharmacology 2006-02, Vol.58 (2), p.195-200
Hauptverfasser: Kinoshita, Natsumi, Takahashi, Tomoko, Tada, Shoko, Shinozuka, Kazumasa, Mizuno, Nobuyasu, Takahashi, Koichi
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container_end_page 200
container_issue 2
container_start_page 195
container_title Journal of pharmacy and pharmacology
container_volume 58
creator Kinoshita, Natsumi
Takahashi, Tomoko
Tada, Shoko
Shinozuka, Kazumasa
Mizuno, Nobuyasu
Takahashi, Koichi
description 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.
doi_str_mv 10.1211/jpp.58.2.0006
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source MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current)
subjects Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - pharmacology
Animals
Dextrans - blood
Dextrans - pharmacokinetics
Fluorescein-5-isothiocyanate - analogs & derivatives
Fluorescein-5-isothiocyanate - pharmacokinetics
Ileum - drug effects
Ileum - metabolism
Intestinal Absorption - drug effects
Male
Nucleotides - pharmacology
Purinergic P2 Receptor Agonists
Purinergic P2 Receptor Antagonists
Pyridoxal Phosphate - analogs & derivatives
Pyridoxal Phosphate - pharmacology
Rats
Rats, Wistar
Receptors, Purinergic P2 - metabolism
Suramin - pharmacology
Thionucleotides - pharmacology
title Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum
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