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

Abstract

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.

Intestinal Inflammation Increases the Expression of the P2Y6 Receptor on Epithelial Cells and the Release of CXC Chemokine Ligand 8 by UDP

“…Under normal conditions, the P2Y 2 , P2Y 4 , and P2Y 6 receptors actively participate in the regulation of Cl Ϫ , Na ϩ , and K ϩ secretion in the small and large intestine (10 -12) as well as in the absorption of watersoluble and high-m.w. compounds from the ileum (13). Under inflammatory conditions, P2Y receptor activation can stimulate cell proliferation, participate in immune cell recruitment, proliferation and differentiation, enhance cytokine and proinflammatory molecule expression and secretion, and increase expression of cell adhesion molecules and cell migration, as has been demonstrated in many other systems (14 -18).…”

“…Enhanced P2Y 1 receptor mRNA expression could also be measured, but was not statistically significant, whereas no difference in the P2Y 4 receptor transcript could be noticed between normal and DSS-treated mice. Although several oligonucleotide primer sets were used, we could not detect transcripts for P2Y 12,13 and P2Y 14 receptors (data not shown), whereas the P2Y 11 receptor gene has not yet been cloned in the mouse or rat. This increase in P2Y 2 and P2Y 6 mRNA receptor expression correlated with an increase in the clinical score with r values of 0.928 and 0.987 ( p Ͻ 0.05) for P2Y 2 and P2Y 6 , respectively.…”

Dynamic recycling of extracellular ATP in human epithelial intestinal cells

“…The consequences of P1 signalling on proliferation of Caco-2 cells and several other intestinal epithelial cell lines have been studied before [28]. In general, the balance between P1 and P2 receptors on epithelial cells regulate intestinal secretion [29][30][31][32] and absorption [33,34]; responses triggered by the P2 receptor stimulation by eATP and other nucleotides are sometimes counteracted by P1 receptor stimulation by adenosine, though the potential role of ecto-AK was not considered in this context.…”

NTPDase1 and -2 are expressed by distinct cellular compartments in the mouse colon and differentially impact colonic physiology and function after DSS colitis

“…[13][14][15]. P2Y 1 receptors mediate relaxations of bowel smooth muscles (35,36,101) while P1 and P2 receptors on epithelial cells regulate intestinal secretion (23,44,60,65) and absorption (59,106). Nucleotides are also important transmitters in the enteric nervous system (ENS) where they mediate fast and slow synaptic transmission (reviewed in Refs.…”