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.
Pflugers Arch
2004 Oct 01;4491:66-75. doi: 10.1007/s00424-004-1293-2.
Show Gene links
Show Anatomy links
Stimulation of Xenopus P2Y1 receptor activates CFTR in A6 cells.
Guerra L
,
Favia M
,
Fanelli T
,
Calamita G
,
Svetlo M
,
Bagorda A
,
Jacobson KA
,
Reshkin SJ
,
Casavola V
.
???displayArticle.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 involvement of this scaffolding protein. Activation or inhibition of PKC had no effect per se on basal Cl- efflux but potentiated or reduced the 2-MeSADP-dependent stimulation of Cl- efflux, respectively. These data suggest that the X laevis P2Y1 receptor in A6 cells can increase both cAMP/PKA and Ca2+/PKC intracellular levels and that the PKC pathway is involved in CFTR activation via potentiation of the PKA pathway.
Abbracchio,
Purinoceptors: are there families of P2X and P2Y purinoceptors?
1994, Pubmed
Abbracchio,
Purinoceptors: are there families of P2X and P2Y purinoceptors?
1994,
Pubmed
Anderson,
Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia.
1991,
Pubmed
Bagorda,
Extracellular adenine nucleotides regulate Na+/H+ exchanger NHE3 activity in A6-NHE3 transfectants by a cAMP/PKA-dependent mechanism.
2002,
Pubmed
,
Xenbase
Bagorda,
Reciprocal protein kinase A regulatory interactions between cystic fibrosis transmembrane conductance regulator and Na+/H+ exchanger isoform 3 in a renal polarized epithelial cell model.
2002,
Pubmed
Banderali,
Control of apical membrane chloride permeability in the renal A6 cell line by nucleotides.
1999,
Pubmed
,
Xenbase
Barnard,
G protein-coupled receptors for ATP and other nucleotides: a new receptor family.
1994,
Pubmed
Beltman,
The selective protein kinase C inhibitor, Ro-31-8220, inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, induces c-Jun expression, and activates Jun N-terminal kinase.
1996,
Pubmed
Brochiero,
Basolateral membrane chloride permeability of A6 cells: implication in cell volume regulation.
1995,
Pubmed
,
Xenbase
Button,
PKC-mediated stimulation of amphibian CFTR depends on a single phosphorylation consensus site. insertion of this site confers PKC sensitivity to human CFTR.
2001,
Pubmed
,
Xenbase
Camaioni,
Deoxyadenosine bisphosphate derivatives as potent antagonists at P2Y1 receptors.
1998,
Pubmed
Carr,
Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79.
1992,
Pubmed
Casavola,
Polarization of adenosine effects on intracellular pH in A6 renal epithelial cells.
1997,
Pubmed
,
Xenbase
Casavola,
Effect of adenosine on Na+ and Cl- currents in A6 monolayers. Receptor localization and messenger involvement.
1996,
Pubmed
Chan,
Extracellular ATP activates both Ca(2+)- and cAMP-dependent Cl- conductances in rat epididymal cells.
1995,
Pubmed
Chappe,
Stimulatory and inhibitory protein kinase C consensus sequences regulate the cystic fibrosis transmembrane conductance regulator.
2004,
Pubmed
Cheng,
cDNA encodes Xenopus P2Y(1) nucleotide receptor: expression at the neuromuscular junctions.
2003,
Pubmed
,
Xenbase
Communi,
Cloning of a human purinergic P2Y receptor coupled to phospholipase C and adenylyl cyclase.
1997,
Pubmed
Dalziel,
Receptors for adenine nucleotides and nucleosides: subclassification, distribution, and molecular characterization.
1994,
Pubmed
Deetjen,
The luminal P2Y receptor in the isolated perfused mouse cortical collecting duct.
2000,
Pubmed
Dubyak,
Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides.
1993,
Pubmed
Dérand,
Activation of VPAC1 receptors by VIP and PACAP-27 in human bronchial epithelial cells induces CFTR-dependent chloride secretion.
2004,
Pubmed
Friedrich,
Activation of potassium channels in renal epithelioid cells (MDCK) by extracellular ATP.
1989,
Pubmed
Grynkiewicz,
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
1985,
Pubmed
Hall,
A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins.
1998,
Pubmed
Harden,
P2-purinergic receptors: subtype-associated signaling responses and structure.
1995,
Pubmed
Henning,
Characterization of P2-purinoceptor mediated cyclic AMP formation in mouse C2C12 myotubes.
1993,
Pubmed
Insel,
P2Y receptors of MDCK cells: epithelial cell regulation by extracellular nucleotides.
2001,
Pubmed
Iwase,
ATP-induced Cl- secretion with suppressed Na+ absorption in rabbit tracheal epithelium.
1997,
Pubmed
Jia,
Phosphorylation by protein kinase C is required for acute activation of cystic fibrosis transmembrane conductance regulator by protein kinase A.
1997,
Pubmed
Klussmann,
Protein kinase A anchoring proteins are required for vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells.
1999,
Pubmed
Köttgen,
P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport.
2003,
Pubmed
,
Xenbase
Lester,
Anchoring and scaffold proteins for kinases and phosphatases.
1997,
Pubmed
Ling,
Expression of the cystic fibrosis phenotype in a renal amphibian epithelial cell line.
1997,
Pubmed
,
Xenbase
Marcet,
Pharmacological and signaling properties of endogenous P2Y1 receptors in cystic fibrosis transmembrane conductance regulator-expressing Chinese hamster ovary cells.
2004,
Pubmed
Marunaka,
Chloride channels in the apical membrane of a distal nephron A6 cell line.
1990,
Pubmed
McCoy,
Nucleotides regulate NaCl transport in mIMCD-K2 cells via P2X and P2Y purinergic receptors.
1999,
Pubmed
Middleton,
Nucleotide receptors regulate membrane ion transport in renal epithelial cells.
1993,
Pubmed
Mori,
ATP-activated cation conductance in a Xenopus renal epithelial cell line.
1996,
Pubmed
,
Xenbase
Nguyen,
P2Y(11), a purinergic receptor acting via cAMP, mediates secretion by pancreatic duct epithelial cells.
2001,
Pubmed
Nilius,
Ca2+ release and activation of K+ and Cl- currents by extracellular ATP in distal nephron epithelial cells.
1995,
Pubmed
O'Reilly,
Purinoceptor activation of chloride transport in cystic fibrosis and CFTR-transfected pancreatic cell lines.
1998,
Pubmed
Ostrom,
Angiotensin II enhances adenylyl cyclase signaling via Ca2+/calmodulin. Gq-Gs cross-talk regulates collagen production in cardiac fibroblasts.
2003,
Pubmed
Paradiso,
Polarized signaling via purinoceptors in normal and cystic fibrosis airway epithelia.
2001,
Pubmed
Post,
ATP activates cAMP production via multiple purinergic receptors in MDCK-D1 epithelial cells. Blockade of an autocrine/paracrine pathway to define receptor preference of an agonist.
1998,
Pubmed
Raghuram,
A kinase-regulated mechanism controls CFTR channel gating by disrupting bivalent PDZ domain interactions.
2003,
Pubmed
Raghuram,
Regulation of cystic fibrosis transmembrane conductance regulator single-channel gating by bivalent PDZ-domain-mediated interaction.
2001,
Pubmed
Reshkin,
Activation of A(3) adenosine receptor induces calcium entry and chloride secretion in A(6) cells.
2000,
Pubmed
Sheppard,
Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents.
1992,
Pubmed
Stutts,
Multiple modes of regulation of airway epithelial chloride secretion by extracellular ATP.
1994,
Pubmed
Verrey,
Antidiuretic hormone action in A6 cells: effect on apical Cl and Na conductances and synergism with aldosterone for NaCl reabsorption.
1994,
Pubmed
,
Xenbase
Woo,
Adenylyl cyclase is involved in desensitization and recovery of ATP-stimulated Cl- secretion in MDCK cells.
1998,
Pubmed
Zambon,
Cloning, expression, signaling mechanisms, and membrane targeting of P2Y(11) receptors in Madin Darby canine kidney cells.
2001,
Pubmed
