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Dr Brian King

  • Telephone:

    020 7472 6563

  • Extension:

    #6 292 x35268

  • Fax:

    020 7472 6476

  • Email:

    b.king@ucl.ac.uk

  • Webpage:

    http://www.ucl.ac.uk/npp/bking.html

  • Address:

    Rooms 1.719-1.721 NPP, Royal Free Campus,
    Hampstead, London,
    WC1E 6BT

  • Appointments:

    Senior Lecturer, Neuroscience, Physiology & Pharmacology, Div of Biosciences

Summary

Brian King graduated in Physiology (1976) and Pharmacology (1980) at the University of Glasgow, Scotland.  The main theme in both degree programmes was synaptic physiology of the peripheral nervous system, allied with research projects on the discovery of novel inhibitory transmitters. His studentship was funded by the MRC.

His first academic appointment was at the Mayo Clinic (Rochester, Minnesota; 1980-85), where he joined the Department of Physiology & Biophysics to study the biophysical and signalling properties of sympathetic neurons innervating the GI tract. After 5 years in the US, Dr. King moved first to McGill University (Montreal, Canada; 1985), then the London Hospital Medical School (London England; 1986-88), to study sensory systems of the GI tract, the gut-brain axis and peptidergic mediators of satiety and hunger.

He took time out of academia to join SmithKline Beecham (1989-92) and study the causes of the Irritable Bowel Syndrome. There, he was involved in the discovery and development of novel antagonists for 5-HT4 receptors, culminating in the discovery of SB204070, to regulate the sensitivity of gut motor & sensory nerves. Returning to academia (UCL;1992), he was immediately involved in the isolation and characterisation of the first of the nucleotide receptors, P2Y1, which is now known to mediate fast IJPs in the gut. 

Dr. King has spent the last 19 years at UCL, studying the purinoceptor family of signalling molecules which now encompasses over 25 receptor subtypes. Dr. King sits on advisory boards for nucleotide signalling (IUPHAR P2X and P2Y Nomenclature Subcommittees) and regularly contributes to the Handbook of Receptor Classification (Sigma RBI) and Guide to Receptors and Channels (Br J Pharmacol).

Research Summary

Nucleotides are naturally occurring compounds found in all living cells, where they have well defined biochemical and physiological roles. The most abundant nucleotide is adenosine 5'-triphosphate (ATP), which occurs in millimolar concentrations in the cytosol and molar concentrations in intracellular storage vesicles. 

Inside the cell, ATP represents the major energy currency for biochemical metabolism. Outside the cell, ATP represents a highly regulated way for cells to talk to each other. ATP and its derivatives can activate a large number of membrane-bound signalling proteins, collectively called the purinoceptor family. All cells possess purinoceptors and typically more than one subtype. As a result, these signalling proteins affect practically every aspect of human physiology.

Dr King works on the signalling properties of the mammalian purinoceptor family, mainly by expressing them in isolation in host cells (Xenopus oocytes or 1321N1 human astrocytoma cells). Sometimes, two or more subunits are expressed together to make heteromeric assemblies of signalling molecules. Occasionally, purinoceptors are co-expressed with other types of signalling proteins to investigate receptor-receptor crosstalk. Already, he and his colleagues have studied how purinoceptors affect TRPV1, ENaC and AQP2 channels.

The results of these cloning experiments are compared with results from parallel studies of tissues and organs containing key members of the purinoceptor family. Dr King works closely with other scientists throughout UCL (and externally), to model signalling systems that employ purinoceptors and investigate unresolved issues in human physiology.

Some of his past studies have focussed the role of extracellular nucleotides in i) bone modelling and osteoporosis, ii) control of breathing, iii) tubule function in kidney, iv) blood platelet function in control of bleeding, v) astrocyte growth following brain injury, vi) signalling in sensory nerve pathways, including the ear, vi) control of the urinary bladder and vii) control of gastrointestinal motility.
 
Recently, Dr King's attention has returned to the gut-brain axis and the control of appetite and satiety by purinergic transmission in motor & sensory nerve pathways connecting the brain to the GI tract.

Research Activities

  • Autonomic Nervous System Sensory and motor innervation of vessels and viscera
  • Autonomic nervous system in health and disease
  • Autonomic neuroscience
  • Autonomic neuroscience/purinergic signalling
  • Integrative physiology
  • Molecular mechanisms involved in pain pathways
  • Nephrology
  • Neurotransmitters in Sensory systems
  • Purinergic Transmission
  • Understanding treatments of bladder dysfunction
  • gastrointestinal tract
  • obesity

Recent Publications

Displaying 50 most recent publications. For the full list please visit UCL Discovery

  1. King BF (2012) Resolution and concordance in dissecting the compound inhibitory junction potential JOURNAL OF PHYSIOLOGY-LONDON, 590(8), 1777 - 1778. 10.1113/jphysiol.2012.230110.
  2. King BF (2012) Resolution and concordance in dissecting the compound IJP J Physiol, 590(8), 1777 - 1778.
  3. King BF,Goodey GC (2011) EVALUATION OF PD20 LUMITESTER FOR MEASUREMENT OF EXTRACELLULAR ATP Purinergic Signalling.
  4. Goodey GC,King BF (2010) P2X receptor activation in normal, high and low extracellular sodium. Purinergic Signalling, 7, 151 - 152.
  5. Bishara S,Gao H,Khasriya R,Lunawat R,Malone-Lee M,Malone-Lee J,King BF (2009) PATIENTS WITH OAB HAVE LONGER MORE CONTRACTED BLADDER MUSCLE CELLS THAN CONTROLS INT UROGYNECOL J, 20, S150 - S151.
  6. Wildman SS,Boone M,Peppiatt-Wildman CM,Contreras-Sanz A,King BF,Shirley DG,Deen PM,Unwin RJ (2009) Nucleotides downregulate aquaporin 2 via activation of apical P2 receptors. J Am Soc Nephrol, 20(7), 1480 - 1490. 10.1681/ASN.2008070686.
  7. Wildman SSP,Kang ESK,King BF (2009) ENaC, renal sodium excretion and extracellular ATP PURINERG SIGNAL, 5(4), 481 - 489. 10.1007/s11302-009-9150-6.
  8. Bishara S,King BF,Malone-Lee J (2009) Isolated detrusor muscles cells lengthen in outflow obstruction BJU INTERNATIONAL, 103, 18 - 18.
  9. Wildman SSP,Marks J,Turner CM,Yew-Booth L,Peppiatt-Wildman CM,King BF,Shirley DG,Wang W,Unwin RJ (2008) Sodium-dependent regulation of renal amiloride sensitive currents by apical P2 receptors. Journal of The American Society of Nephrology, 19, 731 - 742. 10.1681/ASN.2007040443.
  10. Wildman SSP,King BF (2008) P2X receptors: epithelial ion channels and regulators of salt and water transport Nephron Physiology, 108, 60 - 67. 10.1159/000122028.
  11. Wildman SS,Shirley DG,King BF,Unwin RJ (2008) Sodium dependent regulation of ENaC by apical P2 receptors in rat collecting duct: are P2X receptors luminal sodium sensors? Proceedings of the Physiological Society, 9, C3.
  12. Townsend-Nicholson A,Drew CM,Saunders-Wage E,King BF (2008) Modulation of P2Y11 by compounds with activity at guinea-pig taenia coli Purinergic Signalling, 4, S88 - S89.
  13. Bishara S,King BF,Shah PJR,Malone-Lee J,Fry CH (2008) M2 acetylcholine activity reduces with advancing age in the human detrusor Journal of Urology, 179, 131.
  14. Bishara S,Shah PJR,Malone-Lee J,King BF,Fry CH (2008) M2 receptor activation modulates contractions of human detrusor via cAMP inhibition British Journal of Clinical Pharmacology, 65, 978.
  15. King BF,Townsend-Nicholson A (2008) α,β-methyleneATP: a P2Y11 agonist and smooth muscle relaxant Purinergic Signalling, 4, S131.
  16. King BF,Townsend-Nicholson A (2008) Benzoyl-benzoyl-ATP: a smooth muscle relaxant and P2Y11 agonist Purinergic Signalling, 4, S132.
  17. Asatryan L,Popova M,Woodward JJ,King BF,Alkana RL,Davies DL (2008) Roles of ectodomain and transmembrane regions in ethanol and agonist action in purinergic P2X2 and P2X3receptors Neuropharmacology, 55(5), 835 - 843. 10.1016/j.neuropharm.2008.06.044.
  18. King BF,Townsend-Nicholson A (2008) Involvement of P2Y1 and P2Y11 purinoceptors in parasympathetic inhibition of colonic smooth muscle. The Journal of Pharmacology and Experimental Therapeutics, 324(3), 1055 - 1063. 10.1124/jpet.107.131169.
  19. Turner CM,King BF,Srai KS,Unwin RJ (2007) Antagonism of endogenous putative P2Y receptors reduces the growth of MDCK-derived cysts cultured in vitro. American Journal of Physiology, 292, F15 - F25.
  20. Wildman SSP,Turner CM,Marks J,Shirley DG,King BF,Unwin RJ (2007) Differential regulation of renal ENaC by apical P2X and P2Y receptors FASEB JOURNAL, 21(6), A1328 - A1328.
  21. Greenwood D,Jagger DJ,Huang LC,Hoya N,Thorne PR,Wildman SS,King BF,Pak K,Ryan AF,Housley GD (2007) P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea DEVELOPMENT, 134(7), 1407 - 1417. 10.1242/dev.002279.
  22. King BF (2007) Novel P2X7 receptor antagonists ease the pain. British Journal of Pharmacology, 151, 565 - 567.
  23. Greenwood D,Jagger DJ,Huang LC,Hoya N,Thorne PR,Wildman SS,King BF,Pak K,Ryan AF,Housley GD (2007) P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea. Development, 134, 1407 - 1417. 10.1242/dev.002279.
  24. Nicke A,King BF (2006) Heteromerization of P2X receptors, 383 - 417.
  25. King BF (2006) P2 receptors, 130 - 137.
  26. Wildman SS,Turner CM,Marks J,Peppiatt CM,Churchill LJ,Li D,Shirley DG,Wang W,King BF,Unwin RJ (2006) Evidence for P2X receptor-mediated inhibition of sodium reabsorption in collecting ducts from sodium-restricted rats. Proceedings of Physiological Society, 2, PC2.
  27. Housley GD,Greenwood D,Jagger DJ,Hoya N,Huang L-C,Thorne PR,King BF,Wildman SS,Ryan AF (2006) P2X2/3 receptor inhibition of BDNF-mediated spiral ganglion neurite outgrowth..
  28. Wildman SS,Boone M,Peppiatt CM,Churchill LJ,Shirley DG,King BF,Deen PMT,Unwin RJ (2006) Immunofluorescent labelling reveals dDAVP-dependent P2 receptor expression and apical P2 receptor-mediated inhibition of AQP2 expression in mpkCCD(cl4) cultures. Proceeding of Journal of Physiology, 3, C3.
  29. Davies DL,Asatryan L,Kuo SF,Woodward JJ,King BF,Alkana RL,Xiao C,Sun H,Hu XQ,Hayrapetyan V,Lovinger DM,Machu TK (2006) The effects of ethanol on adenosine 5´-triphosphate-gated purinergic and 5-hydroxytryptamine3 receptors Alcoholism: Clinical and Experimental Research, 30, 349 - 358.
  30. Bailey MA,Shirley DG,King BF,Burnstock G,Unwin RJ (2006) Extracellular nucleotides and renal function, 477 - 496.
  31. King BF,Liu M,Townsend-Nicholson A,Burnstock G (2006) Inhibitory interaction between activated TRPV1 and P2X3 receptors Proceedings of the Physiology Society, 3C35.
  32. Chapman E,Hussain S,Peppiatt CM,Marks J,Churchill LJ,Turner CM,King BF,Unwin RJ,Wildman SS (2006) Immunohistochemical localisation of P2 receptors in the rat renal collecting duct:effects of altering dietary sodium intake. Proceedings of Physiological Society, 2, PC7.
  33. Wildman SS,Peppiatt CM,Boone M,Konings I,Marks J,Churchill LJ,Turner CM,Shirley DG,King BF,Deen PMT,Unwin RJ (2006) Possible role of apical P2 receptors in modulating aquaporin-2-mediatiated water reabsorption in the collecting duct. Proceedings of Physiological Society, 2, PC4.
  34. Wildman SS,Marks J,Churchill LJ,Peppiatt CM,Horisburger JD,King BF,Unwin RJ (2005) Molecular cross-talk between epithelial sodium channels and ATP-gated P2X receptors.
  35. Davies DL,Kochegarov AA,Kuo ST,Kulkarni AA,Woodward JJ,King BF,Alkana RL (2005) Ethanol differentially affects ATP-gated P2X(3) and P2X(4) receptor subtypes expressed in Xenopus oocytes NEUROPHARMACOLOGY, 49(2), 243 - 253. 10.1016/j.neuropharm.2005.03.015.
  36. Wildman SS,Marks J,Churchill LJ,Peppiatt CM,Chraibi A,Shirley DG,Horisberger JD,King BF,Unwin RJ (2005) Regulatory interdependence of cloned epithelial Na+ channels and P2X receptors. Journal of the American Society of Nephrology, Sep;16(9), 2586 - 2597.
  37. Davies DL,Kochegarov AA,Kuo S,Kulkarni AA,Woodward JJ,King BF,Arkana RL (2005) Ethanol differentially affects ATP-gated P2X3 and P2X4 receptor subtypes expressed in Xenopus oocytes Neuropharmacology, 49(2), 243 - 253.
  38. King BF,Liu M,Townsend-Nicholson A,Pfister J,Padilla F,Ford AP,Gever JR,Oglesby IB,Schorge S,Burnstock G (2005) Antagonism of ATP responses at P2X receptor subtypes by the pH indicator dye, Phenol red. British Journal of Pharmacology, 145(3), 313 - 322. 10.1038/sj.bjp.0706187.
  39. Wildman SS,Marks J,Churchill LJ,Peppiatt CM,Horisberger J-D,King BF,Unwin RJ (2005) Molecular interactions between cloned epithelial sodium channels and ATP-gated P2X receptors. FASEB, 19(5), A1177.
  40. Abbracchio MP,Burnstock G,Boeynaems J-M,Barnard EA,Boyer JL,Kennedy C,Miras-Portugal MT,King BF,Gachet C,Jacobson KA,Weisman GA (2005) The recently deorphanized GPR80 (GPR99) proposed to be the P2Y15 receptor is not a genuine P2Y receptor Trends in Pharmacological Sciences, 26(1), 8 - 9.
  41. King BF,Knowles ID,Burnstock G,Ramage AG (2004) Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetized rats British Journal of Pharmacology, 142(3), 519 - 530.
  42. Wildman SS,Shirley DG,King BF,Unwin RJ (2004) Indirect evidence for regulation of sodium reabsorption in sodium-restricted rats by an ATP-gated heteromeric P2X receptor. Journal of Physiology, 560P, PC11.
  43. Wildman SS,Shirley DG,King BF,Unwin RJ (2004) Potential regulation of Na+ reabsorption in Na+-restricted rats by an ATP-gated P2X4/6 receptor:pharmacological evidence. Journal of The American Society of Nephrology, 15, F-PO091.
  44. King BF,Townsend-Nicholson A (2003) Nucleotide and nucleoside receptors Tocris Reviews, 23, 1 - 12.
  45. Davies DL,Woodward JJ,King BF,Sribour LM,Alkana RL (2003) Differential ethanol sensitivity between ATP-gated P2X receptor subtypes expressed in both Xenopus oocytes and HEK293 cells.
  46. Abbracchio MP,Boeynaems J-M,Barnard EA,Boyer JL,Kennedy C,Miras-Portugal MT,King BF,Gachet C,Jacobson KA,Weisman GA,Burnstock G (2003) Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family Trends in Pharmacological Sciences, 24(2), 52 - 55.
  47. Wildman SS,Unwin RJ,King BF (2003) Extended pharmacological profiles of rat P2Y2 and rat P2Y4 receptors and their sensitivity to extracellular H+ and Zn2+ ions. British Journal of Pharmacology, 140(7), 1177 - 1186.
  48. Wildman SS,Hooper KM,Turner CM,Sham JS,Lakatta EG,King BF,Unwin RJ,Sutters M (2003) The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl- conductance through increased Ca2+ entry. American Journal of Physiology - Renal Physiology, 285, F1168 - F1178.
  49. King BF,Liu M,Brown SG,Knight G,Townsend-Nicholson A,Dunn PM,Wildman SS,Jackson VM,Cunnane TC,Pfister J,Padilla F,Ford AP,Burnstock G (2003) P2X receptor blockade by the pH indicator dye, Phenol Red Journal of Physiology, 547P, C69.
  50. Wildman SS,King BF,Unwin RJ (2003) Recharacterisation of UTP-sensitive P2Y receptors found in rat kidney Journal of The American Society of Nephrology, 14, SU-PO076.

Biography

Brian King graduated in Physiology (1976) and Pharmacology (1980) at the University of Glasgow, Scotland.  The main theme in both degree programmes was synaptic physiology of the peripheral nervous system, allied with research projects on the discovery of novel inhibitory transmitters. His studentship was funded by the MRC.

His first academic appointment was at the Mayo Clinic (Rochester, Minnesota; 1980-85), where he joined the Department of Physiology & Biophysics to study the biophysical and signalling properties of sympathetic neurons innervating the GI tract. After 5 years in the US, Dr. King moved first to McGill University (Montreal, Canada; 1985), then the London Hospital Medical School (London England; 1986-88), to study sensory systems of the GI tract, the gut-brain axis and peptidergic mediators of satiety and hunger.

He took time out of academia to join SmithKline Beecham (1989-92) and study the causes of the Irritable Bowel Syndrome. There, he was involved in the discovery and development of novel antagonists for 5-HT4 receptors, culminating in the discovery of SB204070, to regulate the sensitivity of gut motor & sensory nerves. Returning to academia (UCL;1992), he was immediately involved in the isolation and characterisation of the first of the nucleotide receptors, P2Y1, which is now known to mediate fast IJPs in the gut. 

Dr. King has spent the last 19 years at UCL, studying the purinoceptor family of signalling molecules which now encompasses over 25 receptor subtypes. Dr. King sits on advisory boards for nucleotide signalling (IUPHAR P2X and P2Y Nomenclature Subcommittees) and regularly contributes to the Handbook of Receptor Classification (Sigma RBI) and Guide to Receptors and Channels (Br J Pharmacol).

Qualifications

  • 1980: Doctor of Philosophy, University of Glasgow
  • 1976: Bachelor of Science (Honours), University of Glasgow

Keywords

  • Appetite
  • Autonomic dysfunction
  • Behaviour
  • Bladder and sexual dysfunction
  • Calcium imaging
  • Cell culture
  • Confocal microscopy
  • Connectivity
  • Eating disorders
  • Eating disorders
  • Electrophysiological recording techniques
  • Electrophysiology
  • Fluorescence microscopy techniques
  • G-protein coupled receptors
  • Gene expression
  • Hearing
  • Histology
  • Immunohistochemistry
  • Integrative physiology
  • Intracellular recording
  • Ion channels
  • Molecular physiology of nucleotide receptors
  • Neural signalling
  • Neuromuscular junction
  • Neuron
  • Neuroscience
  • Obesity
  • Pain
  • Pharmacology
  • Recombinant protein expression
  • Sensory transduction
  • Synapse
  • Xenopus