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Selectivity and activity of adenine dinucleotides at recombinant P2x 2 and P2Y 1 purinoceptors

1996; Wiley; Volume: 119; Issue: 5 Linguagem: Inglês

10.1111/j.1476-5381.1996.tb15771.x

1476-5381

Jesús Pintor, Brian F. King, Marı́a Teresa Miras-Portugal, Geoffrey Burnstock,

Neuroscience of respiration and sleep

British Journal of PharmacologyVolume 119, Issue 5 p. 1006-1012 Free Access Selectivity and activity of adenine dinucleotides at recombinant P2x2 and P2Y1 purinoceptors Jesus Pintor, Jesus Pintor Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT Departamento de Bioquimica, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainSearch for more papers by this authorB.F. King, Corresponding Author B.F. King Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BTDepartment of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BTSearch for more papers by this authorM.T. Miras-Portugal, M.T. Miras-Portugal Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT Departamento de Bioquimica, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainSearch for more papers by this authorG. Burnstock, G. Burnstock Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BTSearch for more papers by this author Jesus Pintor, Jesus Pintor Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT Departamento de Bioquimica, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainSearch for more papers by this authorB.F. King, Corresponding Author B.F. King Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BTDepartment of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BTSearch for more papers by this authorM.T. Miras-Portugal, M.T. Miras-Portugal Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT Departamento de Bioquimica, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainSearch for more papers by this authorG. Burnstock, G. Burnstock Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BTSearch for more papers by this author First published: November 1996 https://doi.org/10.1111/j.1476-5381.1996.tb15771.xCitations: 58 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract 1 Adenine dinucleotides (APxA, × = 2–6) are naturally-occurring polyphosphated nucleotidic substances which are found in the CNS and are known to be released in a calcium-dependent manner from storage vesicles in brain synaptosomes. The selectivity and activity of adenine dinucleotides for neuronally-derived recombinant P2 purinoceptors were studied using P2x2 and P2Y1 subtypes expressed in Xenopus oocytes. 2 For the P2Y1 subtype derived from chick brain, AP3A was equipotent and as active as ATP (EC50 values: 375 ± 86 nM and 334 ± 25 nM, respectively). Ap4A was a weak partial agonist and other dinucleotides were inactive as agonists. None of the inactive dinucleotides were antagonists nor modulated the acitivity of AP3A and ATP. 3 For the P2X2 subtype derived from rat PC12 cells, AP4A was as active as ATP but less potent (EC50 values: 15.2 ± 1 μm and 3.7 ± 0.7 μm, respectively). Other adenosine dinucleotides were inactive as either agonists or antagonists. 4 AP5A (1–100 nM) potentiated ATP-responses at the P2x2 subtype, showing an EC50 of 2.95 ± 0.7 nM for this modulatory effect. AP5A (10 nM) shifted the concentration-response curves for ATP to the left by one-half log10 unit but did not alter the Hill co-efficient for ATP (nH = 2.1 ± 0.1). AP5A (10 nM) failed to potentiate AP4A-responses but did enhance the efficacy of the P2 purinoceptor antagonist, suramin, by 12 fold at the P2x2 subtype. 5 In conclusion, the results show that ionotropic (P2x2) and metabotropic (P2Y1 ATP receptors which occur in the CNS are activated selectively by naturally-occurring adenine dinucleotides which are known to be released with nucleotides from storage vesicles. The observed potentiation of P2x2-responses by AP5A, where co-released with ATP by brain synaptosomes, may have a functional bearing in purinergic signalling in the CNS. References ABBRACCHIO, M.P. & BURNSTOCK, G. (1995). Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol Ther., 64, 445– 475. AKBAR, G.K.M., DASARI, V.R., WEBB, T.E., AYYANATHAN, K., PILLARISETTI, K., SANDHU, A., ATHWAL, R.S., DANIEL, J.L., ASHBY, B., BARNARD, E.A. & KUNAPULI, S.P. (1996). Molecular cloning of a novel P2 purinoceptor from human erythroleukaemic cells. J. Biol. Chem. 271, 18363– 18367. BARISH, M.E. (1983). A transient calcium-dependent chloride current in immature Xenopus oocyte. J. Physiol. 342, 309– 325. BO, X., ZHANG, Y., NASSAR, M., BURNSTOCK, G. & SCHÖEPFER, R. (1995). A P2X purinoceptor cDNA conferring a novel pharmacological profile. FEBS Lett., 375, 129– 133. BRAKE, A.J., WAGENBACH, M.J. & JULIUS, D. (1994). New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature, 371, 519– 523. CASTRO, E., TORRES, M., MIRAS-PORTUGAL, M.T. & GONZALEZ, M.P. (1990). Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells. Br. J. Pharmacol., 100, 360– 364. CHANG, K., HANAOKA, K., KUMADA, M. & TAKUWA, Y. (1995). Molecular cloning and functional analysis of a novel P2 nucleotide receptor. J. Biol Chem. 271, 26152– 26158. CHEN, C., AKOPIAN, A.N., SIVILOTTI, L., COLQUHOUN, D., BURNSTOCK, G. & WOOD, J.N. (1995). A P2X purinoceptor expressed by a subset of sensory neurons. Nature, 311, 428– 431. COLLO, G., NORTH, R.A., KAWASHIMA, E., MERLO-PICH, E., NEIDHART, S., SURPRENANT, A. & BUELL, G. (1996). Cloning of P2X5 and P2X6 receptors, and the distribution and properties of an extended family of ATP-gated ion channels. J. Neurosci. 16, 2495– 2507. COMMUNI, D., PIROTTON, S., PARMENTIER, M. & BOEYNAEMS, J.-M. (1995). Cloning and functional expression of a human uridine nucleotide receptor. J. Biol. Chem., 270, 30849– 30852. DENISENKO, O.N. (1984). Synthesis of diadenosine 5′,5′-P1, P3-triphosphate in yeast at heat shock. FEBS Lett. 178, 149– 152. FEDAN, J.S. & GRANT, L.J.R. (1995). Potentiating and inhibitory effects of periodate-oxydized ATP analogs on contractions of vas deferens to ATP. Eur. J. Pharmacol., 281, 213– 217. FEDAN, J.S. & LAMPORT, S.J. (1990). Two dissociable phases in the contractile response of the guinea-pig vas deferens to adenosine triphosphate. J. Pharmacol. Exp. Ther., 253, 993– 998. GREEN, A.K., COBBOLD, P.H. & DIXON, C.J. (1995). Cytosolic free Ca2+ oscillations by diadenosine 5′,5′′′-P1, P3-triphosphate and diadenosine 5′,5′′′-P1, P4-tetraphosphate in single rat hepatocytes are indistinguishable from those induced by ADP and ATP respectively. Biochem. J. 310, 629– 635. GRUMMT, F. (1978). Diadenosine 5′,5′′′-P1, P4-tetraphosphate triggers initiation of in vitro DNA replication in baby hamster kidney cells. Proc. Natl. Acad. Sci. U.S.A. 75, 371– 377. HOYLE, C.H.V. (1990). Pharmacological activity of adenine dinucleotides in the periphery: possible receptor classes and transmitter function. Gen. Pharmacol., 21, 827– 831. HOYLE, C.H.V. & BURNSTOCK, G. (1992). Actions of purine nucleotides on isolated circular muscle from the human sigmoid colon: evidence for a novel class of purinoceptor. Int. J. Purine Pyrimidine Res., 3, 13. KING, B.F., PINTOR, J., WANG, S., ZIGANSHIN, A.U., ZIGANSHINA, L.E. & BURNSTOCK, G. (1996a). A novel P1 purinoceptor activates an outward K+ current in follicular oocytes of Xenopus laevis. J. Pharmacol. Exp. Ther., 276, 93– 100. KING, B.F., WANG, S. & BURNSTOCK, G. (1995). Two P2 purinoceptor subtypes activate inward current in folliculated oocytes of Xenopus laevis. Br. J. Pharmacol., 116, 50P. KING, B.F., WANG, S. & BURNSTOCK, G. (1996b). P2 purinoceptor-activated inward currents in follicular oocytes of Xenopus laevis. J. Physiol., 494, 17– 28. KING, B.F., ZIGANSHINA, L.E., PINTOR, J. & BURNSTOCK, G. (1996c). Full sensitivity of P2X2 purinoceptor revealed by changing extracellular pH. Br. J. Pharmacol. 111, 1371– 1373. KLISHIN, A., LOZOVAYA, N., PINTOR, J., MIRAS-PORTUGAL, M.T. & KRISHTAL, O.A. (1994). Possible functional role of diadenosine polyphosphates: negative feedback for excitation in hippocampus. Neuroscience, 58, 235– 236. KRISHTAL, O.A., MARCHENKO, S.M., OBUKHOV, A.G. & VOLKOVA, T.M. (1988). Receptors for ATP in rat sensory neurones: the structure-function relationship for ligands. Br. J. Pharmacol., 95, 1057– 1067. LANDAU, E.M. & BLITZER, R.D. (1994). Chloride current assay for phospholipase C in Xenopus oocytes. Methods Enzymol. 238, 140– 154. LAZAROWSKI, E.R., WATT, W.C., STUTTS, M.J., BOUCHER, R.C. & HARDEN, T.K. (1995). Pharmacological selectivity of the human P2U purinoceptor: potent activation by diadenosine tetraphosphate. Br. J. Pharmacol. 116, 1619– 1627. LEWIS, C., NEIDHART, S., HOLY, C., NORTH, R.A., BUELL, G. & SURPRENANT, A. (1995). Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory nuerons. Nature 377, 432– 435. LUSTIG, K.D., SHIAU, A.K., BRAKE, A.J. & JULIUS, D. (1993). Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc. Natl. Acad. Sci. U.S.A., 90, 5113– 5117. LUTHJE, J. & OGILVIE, A. (1983). Diadenosine triphosphate (AP3A) mediates human platelet aggregation by liberation of ADP. Biochem. Biophys. Res. Commun. 115, 253– 260. MacKENZIE, I., KIRKPATRICK, K.A. & BURNSTOCK, G. (1988). Comparative study of the action of AP5A and α, β-methylene ATP on non-adrenergic, non-cholinergic neurogenic excitation in the guinea pig vas deferens. Br. J. Pharmacol. 94, 699– 706. MARCHENKO, S.M., OBUKHOV, A.G., VOLKOVA, T.M. & TARUSOVA, N.B. (1988). Bis (5′adenosyl) tetraphosphate a partial agonist of the ATP receptors on sensory neurons of the rat. Neurofiziologia, 20, 427– 431. McLENNAN, A.G. & ZAMECNIK, P.C. (1992). Dinucleoside polyphosphates - an introduction. In AP4A and other Dinucleoside Polyphosphates. A.G. McLennan pp. 1– 7. Florida: CRC Press. PINTOR, J., DIAZ-REY, M.A. & MIRAS-PORTUGAL, M.T. (1993). AP4A and ADP-β-S binding to P2 purinoceptors present on rat brain synaptic terminals. Br. J. Pharmacol. 108, 1094– 1099. PINTOR, J., DIAZ-REY, M.A., TORRES, M. & MIRAS-PORTUGAL, M.T. (1992a). Presence of diadenosine polyphosphates - AP4A and AP 5A - in rat brain synaptic terminals. Ca2+ dependent release evoked by 4-aminopyridine and veratridine. Neurosci. Lett. 136, 141– 144. PINTOR, J., KOWALEWSKI, H.J., TORRES, M., MIRAS-PORTUGAL, M.T. & ZIMMERMANN, H. (1992b). Synaptic vesicle storage of diadenosine polyphosphates in the Torpedo electric organ. Neurosci. Res. Commun. 10, 9– 14. PINTOR, J. & MIRAS-PORTUGAL, M.T. (1993). Diadenosine polyphosphates -ApnA- as new neurotransmitters. Drug. Devel. Res., 28, 259– 262. PINTOR, J. & MIRAS-PORTUGAL, M.T. (1995a). A novel receptor for diadenosine polyphosphates coupled to the Ca2+ increase in rat brain synaptosomes. Br. J. Pharmacol. 115, 895– 902. PINTOR, J. & MIRAS-PORTUGAL, M.T. (1995b). P2 purinoceptors for diadenosine polyphosphates in the nervous system. Gen. Pharmacol. 26, 229– 235. PINTOR, J., ROTLLÁN, P., TORRES, M. & MIRAS-PORTUGAL, M.T. (1992c). Characterization and quantification of diadenosine hexaphosphate in chromaffin cells: granular storage and secretagogue-induced release. Anal. Biochem., 200, 296– 300. PINTOR, J., TORRES, M., CASTRO, E. & MIRAS-PORTUGAL, M.T. (1991). Characterization of diadenosine tetraphosphate (AP4A) binding sites in cultured chromaffin cells: evidence for a P2Y site. Br. J. Pharmacol. 103, 1980– 1984. RALEVIC, V., HOYLE, C.H.V. & BURNSTOCK, G. (1995). Pivotal role of phosphate chain length in vasoconstrictor versus vasodilator actions of adenine dinucleotides in rat mesenteric arteries. J. Physiol., 483, 703– 713. DEL CASTILLO, A. RODRIGUEZ, TORRES, M., DELICADO, E.G. & MIRAS-PORTUGAL, M.T. (1988). Subcellular distribution studies of diadenosine polyphosphates - AP4A and AP5A- in bovine adrenal medulla: presence in chromaffin granules. J. Neurochem. 51, 1696– 1703. SCHLÜTER, H., OFFERS, E., BRUGGEMANN, G., VAN DER GLET, M., TEPEL, M., NORDHOFF, E., KARAS, M., SPIEKER, C., WITZEL, H. & ZIDEK, W. (1994). Diadenosine polyphosphate and the physiological control of blood pressure. Nature, 361, 186– 188. SCHUBERT, P., PINTOR, J. & MIRAS-PORTUGAL, M.T. (1995). Inhibitor actions of adenosine and adenine dinucleotides in the central nervous system. In Adenosine and Adenine Nucleotides: from Molecular Biology to Integrative Physiology. ed. L. Belardinelli & A. Pelleg pp. 181– 288. Boston, Mass.: Kluwer Academic Publishers. SIMON, J., WEBB, T.E., KING, B.F., BURNSTOCK, G. & BARNARD, E.A. (1995). Characterisation of a recombinant P2Y purinoceptor. Eur. J. Pharmacol. (Mol. Pharmacol. Sect.), 291, 281– 289. STONE, T.W. & PERKINS, M.N. (1981). Adenine dinucleotide effect on rat cortical neurones. Brain Res., 229, 241– 245. SURPRENANT, A., RASSENDREN, F., KAWASHIMA, E., NORTH, R.A. & BUELL, G. (1996). The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272, 735– 738. TEPEL, M., BACHMANN, J., SCHLÜTER, H. & ZIDEK, W. (1996). Diadenosine polyphosphates increase cytosolic calcium and attenuate angiotensin-II-induced changes in calcium in vascular smooth muscle. J. Vase. Res., 33, 132– 138. VALERA, S., HUSSY, N., EVANS, R.J., ADAMI, N., NORTH, R.A., SURPRENANT, A. & BUELL, G. (1994). A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP. Nature, 371, 516– 519. WEBB, T.E., HENDERSON, D., KING, B.F., WANG, S., SIMON, J., BATESON, A.N., BURNSTOCK, G. & BARNARD, E.A. (1996a). A novel G protein-coupled P2 purinoceptor (P2Y3) activated preferentially by nucleoside diphosphates. Mol. Pharmacol., (in press). WEBB, T.E., KAPLAN, M.G. & BARNARD, E.A. (1996b). Identification of 6H1 as a P2Y purinoceptor: P2Y5. Biochem. Biophys. Res. Commun. 219, 105– 110. WEBB, T.E., SIMON, J., KRISHEK, B.J., BATESON, A.N., SMART, T.G., KING, B.F., BURNSTOCK, G. & BARNARD, E.A. (1993). Cloning and functional expression of a brain G-protein coupled ATP receptor. FEBS Lett., 324, 219– 225. WILLIAMS, M. (1994). Purinoceptors nomenclature: challenges for the future. In Adenosine and Adenine Nucleotides: from Molecular Biology to Integrative Physiology, ed. L. Belardinelli & A. Pelleg pp. 39– 48. Boston, Mass.: Kluwer Academic Publishers. ZIGANSHIN, A.U., ZIGANSHINA, L.E., KING, B.F. & BURNSTOCK, G. (1995). Characteristics of ecto-ATPase of Xenopus oocytes and the inhibitory actions of suramin on ATP breakdown. Pflügers Arch. 429, 412– 418. Citing Literature Volume119, Issue5November 1996Pages 1006-1012 ReferencesRelatedInformation