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Geoffery Burnstock’s influence on the evolution of P2X3 receptor pharmacology

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References

  1. Hutchinson AJ, Webb RL, Oei HH, Ghai GR, Zimmerman MB, Williams M (1989) CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity. J Pharmacol Exp Ther 251:47–55

    Google Scholar 

  2. Jarvis MF (1998) Characterization of P1 (adenosine) purinoceptors. In: Enna S, Williams M (eds) Current protocols in pharmacology. Wiley-Liss, New York, pp 19.1–19.15

    Google Scholar 

  3. Jarvis MF, Williams M (1989) Direct autoradiographic localization of adenosine A2 receptors in the rat brain using the A2-selective agonist, [3H] CGS 21680. Eur J Pharmacol 168:243–246

    CAS  PubMed  Google Scholar 

  4. Williams M (1987) Purine receptors in mammalian tissues: pharmacology and physiological significance. Ann Rev Pharmacol Toxicol 27:315–345

    CAS  Google Scholar 

  5. Chen C-C, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN (1995) A P2X purinoceptor expressed by a subset of sensory neurons. Nature (Lond) 377:428–431

    CAS  Google Scholar 

  6. Burnstock G (2012) Purinergic signalling: its unpopular beginning, its acceptance and its exciting future. Bioessay 34:218–225

    CAS  Google Scholar 

  7. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797

    CAS  PubMed  Google Scholar 

  8. Burnstock G, Campbell G, Satchell D, Smythe A (1970) Evidence that adenosine triphosphate or a related nucleotide is the transmitter sub- stance released by non-adrenergic inhibitory nerves in the gut. Br J Pharmacol 40:668–688

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24:509–581

    CAS  PubMed  Google Scholar 

  10. Drury AN, Szent-Gyorgyi A (1929) The physiological activity of adenine compounds with special reference to their action upon the mammalian heart. J Physiol Lond 68:213–237

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Holton P (1959) The liberation of adenosine triphosphate on antidromic stimulation of sensory nerves. J Physiol 145:494–504

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Burnstock G (1978) A basis for distinguishing two types of purinergic receptor. In: Straub RW, Bolis L (eds) Cell membrane receptors for drugs and hormones: a multidisciplinary approach. Raven Press, New York, pp 107–118

    Google Scholar 

  13. Burnstock G, Kennedy C (1985) Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol 16:433–440

    CAS  PubMed  Google Scholar 

  14. Williams M, Jarvis MF (2000) Purinergic and pyrimidinergic receptors as potential drug targets. Biochem Pharmacol 59:1173–1185

    CAS  PubMed  Google Scholar 

  15. Burnstock G (1996) A unifying purinergic hypothesis for the initiation of pain. Lancet 347:1604–1605

    CAS  PubMed  Google Scholar 

  16. Burnstock G, Wood JN (1996) Purinergic receptors: their role in nociception and primary afferent neurotransmission. Curr Opin Neurobiol 6:526–532

    CAS  PubMed  Google Scholar 

  17. Brake A, Schumacher M, Julius D (1996) ATP receptors in sickness and death. Chem Biol 3:229–232

    CAS  PubMed  Google Scholar 

  18. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492

    CAS  PubMed  Google Scholar 

  19. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067

    CAS  PubMed  Google Scholar 

  20. Lewis C, Neidhart S, Holy C, North RA, Buell G, Surprenant A (1995) Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurones. Nature (Lond) 377:432–435

    CAS  Google Scholar 

  21. Cervero F, Laird JM (1996) From acute to chronic pain: mechanisms. Prog Brain Res 110:3–15

    CAS  PubMed  Google Scholar 

  22. Besson JM (1999) The neurobiology of pain. Lancet 353:1610–1615

    CAS  PubMed  Google Scholar 

  23. Woolf CJ, Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288:1765–1769

    CAS  PubMed  Google Scholar 

  24. Scholz J, Woolf CJ (2003) Can we conquer pain? Nat Neurosci Supp 5:1062–1067

    Google Scholar 

  25. Sperlagh B, Vizi ES (1996) Neuronal synthesis, storage and release of ATP. Semin Neurosci 8:175–186

    CAS  Google Scholar 

  26. Burnstock G (2000) P2X receptors on sensory neurons. Br J Anaesth 84:476–488

    CAS  PubMed  Google Scholar 

  27. Cook SP, McCleskey EW (2002) Cell damage excites nociceptors through release of cytosolic ATP. Pain 95:41–47

    CAS  PubMed  Google Scholar 

  28. Kegel B, Braun N, Heine P, Maliszewski CR, Zimmermann H (1997) An ecto-ATPase and an ecto-ATP diphosphohydrolase are expressed in rat brain. Neuropharmacol 36:1189–1201

    CAS  Google Scholar 

  29. Zimmermann H (2000) Extracellular metabolism of ATP and other purines. Naunyn Schmied Arch Pharmacol 362:299–309

    CAS  Google Scholar 

  30. Zimmerman H. Ectonucleotidases. (2001) In Purinergic and pyrimidergic signalling. Handbook of Experimental Pharmacology, Vol. 151, Part 1. Molecular Aspects, Central and Peripheral Nervous System Function. Eds. Abbracchio MP, Williams M. Springer Verlag, Heidelberg, pp. 209–250

  31. Bernier LP, Ase AR, Seguela P (2018) P2X receptor channels in chronic pain pathways. Br J Pharmcol 175:2219–2230

    CAS  Google Scholar 

  32. Jacobson KA, Jarvis MF, Williams M (2002) Purine and pyrimidine (P2) receptors as drug targets. J Med Chem 45:4057–4093

    CAS  PubMed  Google Scholar 

  33. Bland-Ward PA, Humphrey PPA (1997) Acute nociception mediated by hindpaw P2X receptor activation in the rat. Br J Pharmacol 122:366–371

    Google Scholar 

  34. McDonald HA, Bianchi BR, McKenna DG, Briggs CA, Burgard EA, Lynch KJ, Faltynek C, Cartmell J, Jarvis MF (2002) Potent desensitization of human P2X3 receptors by diadenosine polyphosphates, α,β-meATP and ATP. Eur J Pharmacol 435:134–142

    Google Scholar 

  35. Jacobson K, Knutsen L (2001) In Purinergic and pyrimidergic signalling. Handbook of Experimental Pharmacology, Vol. 151, Part 1. Molecular Aspects, Central and Peripheral Nervous System Function. Eds. Abbracchio MP, Williams M Springer Verlag, Heidelberg, 2001, pp. 129–179

  36. Jarvis MF, Wismer CT, Schweitzer E, Yu H, van Biesen T, Lynch KJ, Burgard EC, Kowaluk EA (2001) Modulation of BzATP and formalin induced nociception: attenuation by the P2X receptor antagonist, TNP-ATP and enhancement by the P2X3 allosteric modulator, cibacron blue. Br J Pharmacol 132:259–269

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Alexander K, Niforatos W, Bianchi BR, Burgard EC, Lynch KJ, Kowaluk EA, Jarvis MF, van Biesen T (1999) Allosteric modulation and accelerated resensitization of human P2X3 receptors by cibacron blue. J Pharmacol Exp Ther 291:1135–1142

    CAS  PubMed  Google Scholar 

  38. Bianchi BR, Lynch KJ, Touma E, Niforatos W, Burgard EC, Alexander KM, Park HS, Yu H, Metzger R, Kowaluk EA, Jarvis MF, van Biesen T (1999) Pharmacological characterization of human and rat P2X receptor subtypes. Eur J Pharmacol 376:127–138

    CAS  PubMed  Google Scholar 

  39. Virginio C, Robertson G, Surprenant A, North RA (1998) Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X1, P2X3 and heteromeric P2X2/3 receptors. Mol Pharmacol 53:96–973

    Google Scholar 

  40. Lewis CJ, Surprenant A, Evans RJ (1998) 2’,3’-O-(2,4,6-trinitrophenyl) adenosine 5’-triphosphate (TNP-ATP)-a nanomolar affinity antagonist at rat mesenteric artery P2X receptor ion channels. Br J Pharmacol 124:1463–1466

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Burgard EC, Niforatos W, van Biesen T, Lynch KJ, Kage KL, Touma E, Kowaluk EA, Jarvis MF (2000) Competitive antagonism of recombinant P2X2/3 receptors by 2’,3’-O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate (TNP-ATP). Mol Pharmacol 58:1502–1510

    CAS  PubMed  Google Scholar 

  42. Neelands TR, Burgard EC, Uchic ME, McDonald H, Niforatos W, Faltynek CR, Lynch KJ, Jarvis MF (2003) Electrophysiological and pharmacological properties of a slowly desensitizing chimeric human P2X3 receptor. Br J Pharmacol 140:202–210

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Donnelly-Roberts D, McGaraughty S, Shieh C-C, Honore P, Jarvis MF (2008) Painful purinergic receptors. J Pharm Exp Ther 324(2):409–415

    CAS  Google Scholar 

  44. Jarvis MF, Burgard EC, McGaraughty S, Honore P, Lynch K, Brennan TJ, Subieta A, Van Biesen T, Cartmell J, Bianchi B, Niforatos W, Kage K, Yu H, Mikusa J, Wismer CT, Zhu CZ, Chu K, Lee CH, Stewart AO, Polakowski J, Cox BF, Kowaluk E, Williams M, Sullivan J, Faltynek C (2002) A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci U S A 99:17179–17184

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Jarvis MF, Khakh BS (2009) ATP-gated P2X cation-channels. Neuropharmacol 56:208–215

    CAS  Google Scholar 

  46. Gever JR, Soto R, Henningsen RA, Martin RS, Hackos DH, Panicker S, Rubas W, Oglesby IB, Dillon MP, Milla ME, Burnstock G, Ford APDW (2010) AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist. Br J Pharmacol 160:1387–1398

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Ballini E, Virginio C, Medhurst SJ, Summerfield SG, Aldegheri L, Buson A, Carignani C, Chen YH, Giacometti A, Lago I et al (2011) Characterization of three diaminopyrimidines as potent and selective antagonists of P2X3 and P2X2/3 receptors with in vivo efficacy in a pain model. Br J Pharmacol 163:1315–1325

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Gum R, Wakefield B, Jarvis MF (2012) P2X receptor antagonists for pain management: examination of binding efficiencies and physicochemical properties. Purinergic Signaling 8:41–56

    CAS  Google Scholar 

  49. Marucci G, Ben DD, Buccioni M, Navia AM, Spinaci A et al (2019) Update on novel purinergic P2X3 and P2X2/3 receptor antagonists and their potential therapeutic applications. Exp Op Ther Pat 29:943–963

    CAS  Google Scholar 

  50. Richards D, Gever JD, Ford AP, Fountain SJ (2019) Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. Br J Pharmacol 176:2279–2229

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Ford AP, Udem BJ (2013) The therapeutic promise of ATP antagonism at P2X3 receptors on respiratory and urological disorders. Front Cell Neurosci 7:267

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP et al (2020) Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med 8:775–785

    CAS  PubMed  Google Scholar 

  53. Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L, Hellekant G, Kinnamon SC (2005) ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310:1495–1499

    CAS  PubMed  Google Scholar 

  54. Garceau D, Chauret N (2019) BLU-5937: a selective P2X3 antagonist with potent anti-tussive effect and no taste alteration. Pulmon Pharmcol Ther 56:56–62

    CAS  Google Scholar 

  55. North RA, Jarvis MF (2013) P2X receptors as drug targets. Mol Pharmacol 83:759–769

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Collo G, North RA, Kawashima R, Merlo-Pich E, Neidhart S, Surprenant A (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

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Rae MG, Rowan EG, Kennedy C (1998) Pharmacological properties of P2X3-receptors present in neurons of the rat dorsal root ganglia. Br J Pharmacol 124:176–180

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Llewellyn-Smith IJ, Burnstock G (1998) Ultrastructural localization of P2X3 receptors in rat sensory neurons. Neuroreport 9:2245–2250

    Google Scholar 

  59. Cook SP, Vulchanova L, Hargreaves KM, Elde R, McCleskey EW (1997) Distinct ATP receptors on pain-sensing ans stretch-sensing neurons. Nature (Lond.) 387:505–508

    CAS  Google Scholar 

  60. Burgard EC, Niforatos W, van Biesen T, Lynch KJ, Touma E, Metzger RE, Kowaluk EA, Jarvis MF (1999) P2X receptor-mediated ionic currents in dorsal root ganglion neurons. J Neurophysiol 82:1590–1598

    CAS  PubMed  Google Scholar 

  61. Vulchanova L, Riedl MS, Shuster SJ, Buell G, Suprenant A, North RA, Elde R (1997) Immunohistochemical study of the P2X2 and P2X3 recpetor subunits in rat and monkey sensory neurons and their central terminals. Neuropharmacol 36:1229–1242

    CAS  Google Scholar 

  62. Gu JG, MacDermott AB (1997) Actiavtion of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature (Lond.) 389:749–753

    CAS  Google Scholar 

  63. Coutts AA, Jorizzo JL, Eady RAJ, Greaves MW, Burnstock G (1981) Adenosine triphosphate-evoked vascular changes in human skin: mechanism of action. Eur J Pharmacol 76:391–401

    CAS  PubMed  Google Scholar 

  64. Bleehen T, Keele CA (1977) Observation on the algogenic actions of adenosine compounds on the human blister base preparation. Pain 3:367–377

    CAS  PubMed  Google Scholar 

  65. Hamilton SG, Warburton J, Bhattacharjee A, Ward J, McMahon SB (2000) ATP in human skin elicits a dose-related pain response under conditions of hyperalgesia. Brain 123:1238–1246

    PubMed  Google Scholar 

  66. Holton FA, Holton PJ (1954) The capillary dilator substances in dry powders of spinal roots; a possible role for adenosine triphosphate in chemical transmission from nerve endings. J Physiol 126:124–140

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Jahr CE, Jessell TM (1983) ATP excites a subpopulation of rat dorsal horn neurones. Nature (Lond) 304:730–733

    CAS  Google Scholar 

  68. Hamilton SG, Wade A, McMahon SB (1999) The effects of inflammation and inflammatory mediators on nociceptive behavior induced by ATP analogues in the rat. Br J Pharmacol 126:326–332

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Dowd E, McQueen DS, Chessell IP, Humphrey PPA (1998) P2X receptor-mediated excitation of nociceptive afferents in the normal and arthritic rat knee joint. Br J Pharmacol 125:341–346

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Sawynok J, Reid A (1997) Peripheral adenosine 5’-triphosphate enhances nociception in the formalin test via activation of a purinergic P2X receptor. Eur J Pharmacol 330:115–121

    CAS  PubMed  Google Scholar 

  71. Eriksson J, Bongenheim U, Kidd E, Matthews B, Fried K (1998) Distribution of P2X3 receptors in the rat trigeminal ganglion after inferior alveolar nerve injury. Neurosci Lett 254:37–40

    CAS  PubMed  Google Scholar 

  72. Driessen B, Reimann W, Selve N, Friderichs E, Bultmann R (1994) Antinociceptive effect of intrathecally administered P2-purinoceptor antagonists in rats. Brain Res 666:182–188

    CAS  PubMed  Google Scholar 

  73. Tsuda M, Koizumi S, Kita A, Shigemoto Y, Ueno S, Inoue K (2000) Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin-insensitive primary afferent neurons. J Neurosci 20:RC90 (1-5)

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Liu T, Tracey DJ (2000) ATP P2X receptors play little role in the maintaince of neuropathic hyperalgesia. Neuroreport 11:1669–1672

    CAS  PubMed  Google Scholar 

  75. Honore P, Mikusa J, Cartmell J, McDonald H, Faltynek C, Jarvis MF (2002) Potent blockade of acetic-acid induced abdominal constrictions in mice by the novel P2X receptor antagonist, TNP-ATP. Pain 96:99–105

    CAS  PubMed  Google Scholar 

  76. Tsuzuki K, Kondo E, Fukuoka T, Yi D, Tsujino H, Sakagami M, Noguchi K (2001) Differential regulation of P2X(3) mRNA expression by peripheral nerve injury in intact and injured neurons in the rat sensory ganglia. Pain 91:351–360

    CAS  PubMed  Google Scholar 

  77. Bradbury EJ, Burnstock G, McMahon SB (1998) The expression of P2X3 purinoceptors in sensory neurons: effects of axotomy and glial-derived neurotophic factor. Mol Cel Neurosci 12:256–268

    CAS  Google Scholar 

  78. Novakovic SD, Kassotakis LC, Olgesby IB, Smith JAM, Eglen RM, Ford APDW, Hunter JC (1999) Immunocytochemical localization of P2X3 purinoceptors in sensory neurons in naïve rats and following neuropathic injury. Pain 80:273–282

    CAS  PubMed  Google Scholar 

  79. Kage K, Niforatos W, Zhu CZ, Lynch KJ, Burgard EC, Honore P, Faltynek C, Jarvis MF (2002) Alteration of dorsal root ganglion P2X3 receptor expression and function following spinal nerve ligation in rats. Exp Brain Res 147:511–519

    CAS  PubMed  Google Scholar 

  80. Cockayne DA, Hamilton SG, Zhu Q-M, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford APDW (2000) Urinary bladder hyporeflexia and reduced pain-related behavior in P2X3-deficient mice. Nature (Lond.) 407:1011–1015

    CAS  Google Scholar 

  81. Souslova V, Cesare P, Ding Y, Akoplan AN, Stanfa L, Suzuki R, Carpenter K, Dickenson A, Boyce S, Hill R, Nebenius-Dosthuizan SAJH, Kidd EJ, Wood J (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature (Lond.) 407:1015–1017

    CAS  Google Scholar 

  82. Gingrich JA, Hen R (2000) The broken mouse: the role of development, plasticity and environment in the interpretation of phenotypic changes in knockout mice. Curr Opin Neurobiol 10:146–152

    CAS  PubMed  Google Scholar 

  83. Shimizu I, Iida T, Guan Y, Zhao C, Raja SN, Jarvis MF, Cockayne DA, Caterina MJ (2005) Enhanced thermal avoidance in mice lacking the ATP receptor P2X3. Pain 116:96–108

    CAS  PubMed  Google Scholar 

  84. Honore P, Kage K, Mikusa J, Watt A, Johnston JF, Wyatt J, Faltynek C, Jarvis MF (2002) Analgesic profile of intrathecal P2X3 antisense oligonucleotide treatment in rats. Pain. 99:19–27

    Google Scholar 

  85. Barclay J, Patel A, Dorn G, Wotherspoon G, Moffatt S, Eunson L, Abdel’al S, Natt F, Hall J, Winter J, Bevan S, Wishart W, Fox A, Ganju P (2002) Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain. J Neurosci 22:8139–8147

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA (2015) P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet 385:1198–1205

    CAS  PubMed  Google Scholar 

  87. Mansoor SE, Lu W, Oosterheert W, Shekhar M, Tajkhorshid E, Gouaux E (2016) X-ray structures define human P2X3 receptor gating cycle and antagonist action. Nature 538:66–71

    CAS  PubMed  PubMed Central  Google Scholar 

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Jarvis, M.F. Geoffery Burnstock’s influence on the evolution of P2X3 receptor pharmacology. Purinergic Signalling 17, 33–39 (2021). https://doi.org/10.1007/s11302-020-09744-9

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