The distribution of purinergic receptors, P2Y and P2X, expression within the intestine

Am J Physiol Gastrointest Liver Physiol. 2023 Nov 21. doi: 10.1152/ajpgi.00108.2023. Online ahead of print.ABSTRACTNucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), while the nucleotides ADP, ATP, UTP and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. Since epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond to extracellular nucleotide signals. Using the Human Protein Atlas and Gut Cell Survey, we queried single cell RNA sequencing (RNAseq) data for the P2 purinergic receptors in the small and large intestine. In silico analysis reveals robust mRNA expression of P2RY1, P2RY2, P2RY11 and P2RX4 throughout the gastrointestinal tract. Human intestinal organoids exhibited a similar expression pattern with prominent expression of P2RY1, P2RY2 and P2RX4, but this purinergic receptor repertoire was not conserved in T84, Caco2 and HT29 intestinal epithelial cell lines. Finally, P2YR1 and P2YR2 agonist elicited robust calcium responses in human...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research