Stimulation of Xenopus P2Y1 receptor activates CFTR in A6 cells

Pflügers Archiv : European journal of physiology
L GuerraV Casavola

Abstract

Nucleotide binding to purinergic P2Y receptors contributes to the regulation of a variety of physiological functions in renal epithelial cells. Here, we investigate the regulatory mechanism of the P2Y1 receptor agonist 2-methylthioadenosine diphosphate (2-MeSADP) on Cl- transport in A6 cells, a commonly used model of the distal section of the Xenopus laevis nephron. Protein and mRNA expression analysis together with functional measurements demonstrated the basolateral location of the Xenopus P2Y1 receptor. 2-MeSADP increased intracellular [Ca2+] and cAMP and Cl- efflux, responses that were all inhibited by the specific P2Y1 receptor antagonist MRS 2179. Cl- efflux was also inhibited by the cystic fibrosis transmembrane conductance regulator (CFTR) blocker glibenclamide. Inhibition of either protein kinase A (PKA) or the binding between A-kinase-anchoring proteins (AKAPs) and the regulatory PKA RII subunit blocked the 2-MeSADP-induced activation of CFTR, suggesting that PKA mediates P2Y1 receptor regulation of CFTR through one or more AKAPs. Further, the truncation of the PDZ1 domain of the scaffolding protein Na+/H+ exchanger regulatory factor-2 (NHERF-2) inhibited 2-MeSADP-dependent stimulation of Cl- efflux, suggesting the in...Continue Reading

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Citations

Feb 15, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Laszlo KölesPeter Illes
Mar 25, 2009·Purinergic Signalling·Matthew A Bailey, David G Shirley
Aug 30, 2011·Pharmacological Reviews·Juan A Ardura, Peter A Friedman
Nov 23, 2013·Purinergic Signalling·Geoffrey BurnstockMatthew A Bailey
May 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sami R FamRandy A Hall
Jul 17, 2008·Journal of Neurochemistry·Jun-Wei ZengHuai-Zhen Ruan
Oct 26, 2005·Journal of Cellular Physiology·Melissa L PalmerScott M O'Grady

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