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1. Two molecularly distinct rat P2Y receptors activated equally by adenosine-5'-triphosphate (ATP) and uridine-5'-triphosphate (UTP) (rP2Y2 and rP2Y4 receptors) were expressed in Xenopus oocytes and studied extensively to find ways to pharmacologically distinguish one from the other. 2. Both P2Y subtypes were activated fully by a number of nucleotides. Tested nucleotides were equipotent at rP2Y4 (ATP=UTP=CTP=GTP=ITP), but not at rP2Y2 (ATP=UTP>CTP>GTP>ITP). For dinucleotides (ApnA, n=2-6), rP2Y4 was only fully activated by Ap4A, which was as potent as ATP. All tested dinucleotides, except for Ap2A, fully activated rP2Y2, but none were as potent as ATP. ATP gamma S and BzATP fully activated rP2Y2, whereas ATP gamma S was a weak agonist and BzATP was inactive (as an agonist) at rP2Y4 receptors. 3. Each P2Y subtype showed different sensitivities to known P2 receptor antagonists. For rP2Y2, the potency order was suramin>PPADS= RB-2>TNP-ATP and suramin was a competitive antagonist (pA2, 5.40). For rP2Y4, the order was RB-2>suramin>PPADS> TNP-ATP and RB-2 was a competitive antagonist (pA2, 6.43). Also, BzATP was an antagonist at rP2Y4 receptors. 4. Extracellular acidification (from pH 8.0 to pH 5.5) enhanced the potency of ATP and UTP by 8-10-fold at rP2Y4 but did not affect agonist responses at rP2Y2 receptors. 5. Extracellular Zn2+ ions (0.1-300 microM) coapplied with ATP inhibited agonist responses at rP2Y4 but not at rP2Y2 receptors. 6. These two P2Y receptors differ significantly in terms of agonist and antagonist profiles, and the modulatory activities of extracellular H+ and Zn2+ ions. These pharmacological differences will help to distinguish between rP2Y2 and rP2Y4 receptors, in vivo.
Abbracchio,
Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family.
2003, Pubmed
Abbracchio,
Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family.
2003,
Pubmed Barnard,
G protein-coupled receptors for ATP and other nucleotides: a new receptor family.
1994,
Pubmed Bogdanov,
Molecular cloning and characterization of rat P2Y4 nucleotide receptor.
1998,
Pubmed
,
Xenbase Brooks,
Bound and determined: a computer program for making buffers of defined ion concentrations.
1992,
Pubmed Charlton,
Cloned and transfected P2Y4 receptors: characterization of a suramin and PPADS-insensitive response to UTP.
1996,
Pubmed Clyne,
Mutational analysis of the conserved cysteines of the rat P2X2 purinoceptor.
2002,
Pubmed
,
Xenbase Clyne,
The role of histidine residues in modulation of the rat P2X(2) purinoceptor by zinc and pH.
2002,
Pubmed
,
Xenbase Communi,
Pharmacological characterization of the human P2Y11 receptor.
1999,
Pubmed Communi,
Cloning and functional expression of a human uridine nucleotide receptor.
1995,
Pubmed Dubyak,
Signal transduction by P2-purinergic receptors for extracellular ATP.
1991,
Pubmed Dubyak,
Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides.
1993,
Pubmed Erb,
Functional expression and photoaffinity labeling of a cloned P2U purinergic receptor.
1993,
Pubmed Erb,
Site-directed mutagenesis of P2U purinoceptors. Positively charged amino acids in transmembrane helices 6 and 7 affect agonist potency and specificity.
1995,
Pubmed Filippov,
Coupling of the nucleotide P2Y4 receptor to neuronal ion channels.
2003,
Pubmed Freissmuth,
G protein antagonists.
1999,
Pubmed Hiley,
Effects of pH on responses to adenosine, CGS 21680, carbachol and nitroprusside in the isolated perfused superior mesenteric arterial bed of the rat.
1995,
Pubmed Kenakin,
Drug efficacy at G protein-coupled receptors.
2002,
Pubmed Kennedy,
ATP, an agonist at the rat P2Y(4) receptor, is an antagonist at the human P2Y(4) receptor.
2000,
Pubmed King,
P2 purinoceptor-activated inward currents in follicular oocytes of Xenopus laevis.
1996,
Pubmed
,
Xenbase King,
Full sensitivity of P2X2 purinoceptor to ATP revealed by changing extracellular pH.
1996,
Pubmed
,
Xenbase King,
Metabotropic receptors for ATP and UTP: exploring the correspondence between native and recombinant nucleotide receptors.
1998,
Pubmed Lazarowski,
Cloning and functional characterization of two murine uridine nucleotide receptors reveal a potential target for correcting ion transport deficiency in cystic fibrosis gallbladder.
2001,
Pubmed Lustig,
A nucleotide receptor in vascular endothelial cells is specifically activated by the fully ionized forms of ATP and UTP.
1992,
Pubmed Lustig,
Expression cloning of an ATP receptor from mouse neuroblastoma cells.
1993,
Pubmed
,
Xenbase Mundell,
Evidence for co-expression and desensitization of A2a and A2b adenosine receptors in NG108-15 cells.
1998,
Pubmed Nguyen,
Cloning, expression, and chromosomal localization of the human uridine nucleotide receptor gene.
1995,
Pubmed O'Connor,
Further subclassification of ATP receptors based on agonist studies.
1991,
Pubmed Parr,
Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy.
1994,
Pubmed Pendergast,
Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5'-polyphosphates.
2001,
Pubmed Pintor,
Diadenosine polyphosphate-activated inward and outward currents in follicular oocytes of Xenopus laevis.
1996,
Pubmed
,
Xenbase Ralevic,
Receptors for purines and pyrimidines.
1998,
Pubmed Seye,
Overexpression of P2Y2 purinoceptor in intimal lesions of the rat aorta.
1997,
Pubmed Smart,
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.
1994,
Pubmed Suarez-Huerta,
Molecular cloning and characterization of the mouse P2Y4 nucleotide receptor.
2001,
Pubmed van der Weyden,
Pharmacological characterisation of the P2Y11 receptor in stably transfected haematological cell lines.
2000,
Pubmed Vigne,
Benzoyl ATP is an antagonist of rat and human P2Y1 receptors and of platelet aggregation.
1999,
Pubmed von Kügelgen,
Evidence for a vasoconstriction-mediating receptor for UTP, distinct from the P2 purinoceptor, in rabbit ear artery.
1987,
Pubmed Webb,
Molecular cloning and characterization of the rat P2Y4 receptor.
1998,
Pubmed Wildman,
Zn2+ modulation of ATP-responses at recombinant P2X2 receptors and its dependence on extracellular pH.
1998,
Pubmed
,
Xenbase Zambon,
P2Y(2) receptor of MDCK cells: cloning, expression, and cell-specific signaling.
2000,
Pubmed
