Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-5790
J Clin Invest 2003 Feb 01;1113:371-9. doi: 10.1172/JCI16711.
Show Gene links Show Anatomy links

P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport.

Köttgen M , Löffler T , Jacobi C , Nitschke R , Pavenstädt H , Schreiber R , Frische S , Nielsen S , Leipziger J .


???displayArticle.abstract???
Extracellular nucleotides are important regulators of epithelial ion transport. Here we investigated nucleotide-mediated effects on colonic NaCl secretion and the signal transduction mechanisms involved. Basolateral UDP induced a sustained activation of Cl(-) secretion, which was completely inhibited by 293B, a specific inhibitor of cAMP-stimulated basolateral KCNQ1/KCNE3 K(+) channels. We therefore speculated that a basolateral P2Y(6) receptor could increase cAMP. Indeed UDP elevated cAMP in isolated crypts. We identified an epithelial P2Y(6) receptor using crypt [Ca(2+)](i) measurements, RT-PCR, and immunohistochemistry. To investigate whether the rat P2Y(6)elevates cAMP, we coexpressed the P2Y(1) or P2Y(6) receptor together with the cAMP-regulated cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel in Xenopus oocytes. A two-electrode voltage clamp was used to monitor nucleotide-induced Cl(-) currents. In oocytes expressing the P2Y(1) receptor, ATP transiently activated the endogenous Ca(2+)-activated Cl(-) current, but not CFTR. In contrast, in oocytes expressing the P2Y(6)receptor, UDP transiently activated the Ca(2+)-activated Cl(-) current and subsequently CFTR. CFTR Cl(-) currents were identified by their halide conductance sequence. In summary we find a basolateral P2Y(6) receptor in colonic epithelial cells stimulating sustained NaCl secretion by way of a synergistic increase of [Ca(2+)](i) and cAMP. In support of these data P2Y(6) receptor stimulation differentially activates CFTR in Xenopus oocytes.

???displayArticle.pubmedLink??? 12569163
???displayArticle.pmcLink??? PMC151859
???displayArticle.link??? J Clin Invest


Species referenced: Xenopus
Genes referenced: camp cftr kcne3 kcnq1 p2ry6

References [+] :
Bailey, Evidence for basolateral P2Y(6) receptors along the rat proximal tubule: functional and molecular characterization. 2001, Pubmed