G J Sanger

Summary

Affiliation: GlaxoSmithKline Research and Development
Country: USA

Publications

  1. ncbi request reprint The prokinetic-like activity of ghrelin in rat isolated stomach is mediated via cholinergic and tachykininergic motor neurones
    Anna K Bassil
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, UK
    Eur J Pharmacol 544:146-52. 2006
  2. doi request reprint Development of drugs for gastrointestinal motor disorders: translating science to clinical need
    G J Sanger
    Immuno Inflammatory CEDD, GlaxoSmithKline, Stevenage, Hertfordshire, UK
    Neurogastroenterol Motil 20:177-84. 2008
  3. ncbi request reprint Drugs targeting functional bowel disorders: insights from animal studies
    Gareth J Sanger
    Neurology and Gastroenterology CEDD, GlaxoSmithKline, Harlow, Essex, UK
    Curr Opin Pharmacol 2:678-83. 2002
  4. doi request reprint Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders
    Gareth J Sanger
    Immuno Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK
    Nat Rev Drug Discov 7:241-54. 2008
  5. doi request reprint Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases
    Gareth J Sanger
    ImmunoInflammatory CEDD, GlaxoSmithKline, Stevenage, Herts, UK
    Drug Discov Today 13:234-9. 2008
  6. doi request reprint 5-hydroxytryptamine and the gastrointestinal tract: where next?
    Gareth J Sanger
    Immuno Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Stevenage, Hertfordshire, SG1 2NY, UK
    Trends Pharmacol Sci 29:465-71. 2008
  7. doi request reprint GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility
    G J Sanger
    Immuno Inflammation CEDD, GlaxoSmithKline, Stevenage, UK
    Neurogastroenterol Motil 21:657-64, e30-1. 2009
  8. ncbi request reprint The role of endogenous opioids in the control of gastrointestinal motility: predictions from in vitro modelling
    G J Sanger
    Neurology and Gastroenterology CEDD, GlaxoSmithKline, Harlow, Essex, UK
    Neurogastroenterol Motil 16:38-45. 2004
  9. ncbi request reprint Defensive and pathological functions of the gastrointestinal NK3 receptor
    Gareth J Sanger
    GlaxoSmithKline, Harlow, Essex, UK
    Vascul Pharmacol 45:215-20. 2006
  10. pmc Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation
    N B Dass
    Gastrointestinal Research, Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, UK
    Br J Pharmacol 150:502-8. 2007

Collaborators

Detail Information

Publications45

  1. ncbi request reprint The prokinetic-like activity of ghrelin in rat isolated stomach is mediated via cholinergic and tachykininergic motor neurones
    Anna K Bassil
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, UK
    Eur J Pharmacol 544:146-52. 2006
    ..Ghrelin facilitates both cholinergic and tachykininergic excitatory pathways, consistent with activity within the enteric nervous system and possibly the vagus nerve...
  2. doi request reprint Development of drugs for gastrointestinal motor disorders: translating science to clinical need
    G J Sanger
    Immuno Inflammatory CEDD, GlaxoSmithKline, Stevenage, Hertfordshire, UK
    Neurogastroenterol Motil 20:177-84. 2008
    ..Only then can disease-related ideas be properly tested and drugs brought forward for these disorders (with high clinical need) and then, if successful for IBS and FD...
  3. ncbi request reprint Drugs targeting functional bowel disorders: insights from animal studies
    Gareth J Sanger
    Neurology and Gastroenterology CEDD, GlaxoSmithKline, Harlow, Essex, UK
    Curr Opin Pharmacol 2:678-83. 2002
    ..These targets include receptors for tachykinins, motilin, ghrelin, corticotropin-releasing factor and somatostatin...
  4. doi request reprint Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders
    Gareth J Sanger
    Immuno Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK
    Nat Rev Drug Discov 7:241-54. 2008
    ..The gut-brain axis may therefore provide a range of therapeutic opportunities that deliver a more holistic treatment of upper gastrointestinal disorders...
  5. doi request reprint Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases
    Gareth J Sanger
    ImmunoInflammatory CEDD, GlaxoSmithKline, Stevenage, Herts, UK
    Drug Discov Today 13:234-9. 2008
    ..Recently, additional peptides have been identified from preproghrelin (obestatin) and prepromotilin. These exert biological activity but their pathophysiological significance is unknown...
  6. doi request reprint 5-hydroxytryptamine and the gastrointestinal tract: where next?
    Gareth J Sanger
    Immuno Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Stevenage, Hertfordshire, SG1 2NY, UK
    Trends Pharmacol Sci 29:465-71. 2008
    ....
  7. doi request reprint GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility
    G J Sanger
    Immuno Inflammation CEDD, GlaxoSmithKline, Stevenage, UK
    Neurogastroenterol Motil 21:657-64, e30-1. 2009
    ..Simplification of the structural requirements to activate this receptor greatly facilitates the design of potentially new medicines for gastroparesis...
  8. ncbi request reprint The role of endogenous opioids in the control of gastrointestinal motility: predictions from in vitro modelling
    G J Sanger
    Neurology and Gastroenterology CEDD, GlaxoSmithKline, Harlow, Essex, UK
    Neurogastroenterol Motil 16:38-45. 2004
    ..Consequently, drugs that antagonize opioid receptors may exert prokinetic activity in conditions where intestinal motility is reduced, such as constipation. Further work is required to elucidate the opiate receptor(s) involved...
  9. ncbi request reprint Defensive and pathological functions of the gastrointestinal NK3 receptor
    Gareth J Sanger
    GlaxoSmithKline, Harlow, Essex, UK
    Vascul Pharmacol 45:215-20. 2006
    ..NK(3) receptor biology is, therefore, revealing a novel pathway by which disruptions in intestinal motility and nociception can be induced...
  10. pmc Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation
    N B Dass
    Gastrointestinal Research, Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, UK
    Br J Pharmacol 150:502-8. 2007
    ..The neuromedin U (NMU) receptors, NMU1 and NMU2, are expressed in the gut but their functions are unclear. This study explores the role of NMU in gastrointestinal motility...
  11. ncbi request reprint Modulation of peristalsis by NK3 receptor antagonism in guinea-pig isolated ileum is revealed as intraluminal pressure is raised
    G J Sanger
    Neurology and Gastrointestinal CEDD, GlaxoSmithKline, 3rd Avenue, Harlow, Essex CM19 5AW, UK
    Auton Autacoid Pharmacol 27:105-11. 2007
    ..5. The data suggest that NK(3) receptors are not involved in the modulation of peristaltic movements by physiological stimuli, but they may have a role in modulation of reflexes in extreme or pathological conditions...
  12. pmc The effects of SB 204070, a highly potent and selective 5-HT4 receptor antagonist, on guinea-pig distal colon
    K A Wardle
    SmithKline Beecham Pharmaceuticals, Harlow, Essex
    Br J Pharmacol 112:789-94. 1994
    ..6. SB 204070 is a highly potent, highly selective 5-HT4 receptor antagonist and as such is an important new tool in evaluating the functional role of the 5-HT4 receptor...
  13. pmc Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon
    A K Bassil
    Immuno Inflammation Centre of Excellence for Drug Discovery CEDD, GlaxoSmithKline, Stevenage, UK
    Br J Pharmacol 154:126-35. 2008
    ..As lubiprostone may also directly modulate gastrointestinal motility, we investigated its actions and the possible involvement of prostaglandin EP receptor activation on rat and human isolated gastrointestinal preparations...
  14. pmc The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694
    J Bermudez
    Beecham Pharmaceuticals Research Division, Harlow, Essex, UK
    Br J Cancer 58:644-50. 1988
    ..The potent anti-emetic activity of BRL 43694 is discussed in terms of potential clinical use, and of the fundamental role that 5-HT3 receptors may play in the mechanisms of nausea and vomiting...
  15. doi request reprint 5-hydroxyindalpine, an agonist at the putative 5-HT receptor, has no activity on human recombinant monoamine receptors but accelerates distension-induced peristalsis in mouse isolated colon
    N A Mitchell
    Immuno Inflammation Centre of Excellence in Drug Discovery, GlaxoSmithKline, Stevenage, UK
    Neurogastroenterol Motil 21:760-e48. 2009
    ..However, the absence of an effect of 5-OHIP on a range of different monoamine receptors continues to highlight the need to investigate the identity of the putative 5-HT(1P) receptor...
  16. ncbi request reprint Rank-order inhibition by omega-conotoxins in human and animal autonomic nerve preparations
    G J Sanger
    Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
    Eur J Pharmacol 388:89-95. 2000
    ....
  17. doi request reprint Synergy between 5-HT4 receptor activation and acetylcholinesterase inhibition in human colon and rat forestomach
    S Cellek
    Neurology and Gastroenterology Centre of Excellence in Drug Discovery, GlaxoSmithKline, Harlow, Essex, UK
    Neurogastroenterol Motil 20:539-45. 2008
    ..The results suggest that a synergy between 5-HT4 receptor agonism and AChE inhibition could be established pharmacologically which could be utilized as a novel prokinetic approach to functional GI disorders...
  18. pmc Differences between 5-HT3 receptor antagonists in modulation of visceral hypersensitivity
    S E Banner
    SmithKline Beecham Pharmaceuticals, Harlow, Essex
    Br J Pharmacol 114:558-62. 1995
    ..However, the rank order of antagonist potency does not correlate with their order of potency against the classically defined 5-HT3 receptor...
  19. pmc Inhibition of colonic motility and defecation by RS-127445 suggests an involvement of the 5-HT2B receptor in rodent large bowel physiology
    A K Bassil
    Immuno Inflammation CEDD, GlaxoSmithKline, Stevenage, UK
    Br J Pharmacol 158:252-8. 2009
    ..To explore the role of these receptors, we further characterized the 5-HT(2B) receptor antagonist RS-127445 and studied its effects on peristalsis and defecation...
  20. ncbi request reprint 5-HT4 receptor agonists enhance both cholinergic and nitrergic activities in human isolated colon circular muscle
    S Cellek
    Neurology and Gastroenterology Centre of Excellence in Drug Discovery, GlaxoSmithKline, Harlow, Essex, UK
    Neurogastroenterol Motil 18:853-61. 2006
    ....
  21. ncbi request reprint The relationship between the effects of short-chain fatty acids on intestinal motility in vitro and GPR43 receptor activation
    N B Dass
    Department of Gastrointestinal Research, GlaxoSmithKline, Harlow, UK
    Neurogastroenterol Motil 19:66-74. 2007
    ..In conclusion, SCFAs can modulate intestinal motility, but these effects can be independent of the GPR43 receptor...
  22. pmc Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract
    A K Bassil
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, UK
    Br J Pharmacol 150:58-64. 2007
    ..Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated...
  23. ncbi request reprint Hypersensitivity and hyperreactivity in the irritable bowel syndrome: An opportunity for drug discovery
    G J Sanger
    Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK
    Dig Dis 17:90-9. 1999
    ..Thus, by developing a rational process the pharmaceutical industry may better understand how to design truly effective drugs for the treatment of IBS...
  24. pmc The guinea-pig distal colon--a sensitive preparation for the investigation of 5-HT4 receptor-mediated contractions
    K A Wardle
    SmithKline Beecham Pharmaceuticals, Harlow, Essex
    Br J Pharmacol 110:1593-9. 1993
    ..Furthermore, of the models of this receptor described in the literature, the guinea-pig distal colon appears to be the most sensitive model to date, making it a useful tool in the investigation of 5-HT4 receptor-mediated events...
  25. pmc Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis
    W D Miner
    Beecham Pharmaceuticals Research Division, Harlow, Essex, UK
    Br J Cancer 56:159-62. 1987
    ..These results are discussed in terms of a fundamental role for 5-HT3 receptors in the mechanisms mediating severely emetogenic cancer treatment therapies...
  26. pmc The rabbit motilin receptor: molecular characterisation and pharmacology
    N B Dass
    Department of Gastrointestinal Research, Neurology and Gastroenterology Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
    Br J Pharmacol 140:948-54. 2003
    ....
  27. ncbi request reprint Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin
    N B Dass
    Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, UK
    Neuroscience 120:443-53. 2003
    ..Moreover, we suggest that this activity of ghrelin is mediated via the enteric nervous system, in addition to known vagus nerve-dependent mechanisms...
  28. ncbi request reprint Behavioural and hypothalamic molecular effects of the anti-cancer agent cisplatin in the rat: A model of chemotherapy-related malaise?
    N M Malik
    Division of Basic Medical Sciences, St George s University of London, London, SWl7 ORE, Harlow, Essex CMl9 5AW, UK
    Pharmacol Biochem Behav 83:9-20. 2006
    ..Findings are discussed in relation to the neuropharmacology of chemotherapy-induced malaise...
  29. doi request reprint Increased plasma ghrelin following infliximab in Crohn's disease
    E Z H Sung
    University Hospital, Coventry Unit for Diabetes and Metabolism, University of Warwick, Coventry Neurology Harlow, UK and Immunoinflammatory Centre of Excellence in Drug Discovery, GlaxoSmithKline, Stevenage, UK
    Aliment Pharmacol Ther 29:83-9. 2009
    ..Ghrelin, a potent orexigenic peptide produced by the stomach, may be affected by circulating inflammatory mediators...
  30. pmc Endocannabinoids and the gastrointestinal tract: what are the key questions?
    G J Sanger
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Harlow, UK
    Br J Pharmacol 152:663-70. 2007
    ..Q1: Are CB2 receptors the interface between colonic bacteria and enteric- or extrinsic nerve sensitivity? Relevance of endocannabinoids to humans. Perhaps apart from appetite, this is largely unknown...
  31. ncbi request reprint GABA(B) receptor function in the ileum and urinary bladder of wildtype and GABA(B1) subunit null mice
    G J Sanger
    Department of Gastrointestinal Research, Neurology and GI CEDD, GlaxoSmithKline Pharmaceuticals, Harlow, Essex, UK, CM19 5AW
    Auton Autacoid Pharmacol 22:147-54. 2002
    ....
  32. ncbi request reprint Differential effects of dexamethasone, ondansetron and a tachykinin NK1 receptor antagonist (GR205171) on cisplatin-induced changes in behaviour, food intake, pica and gastric function in rats
    Nasser M Malik
    Division of Basic Medical Sciences, St George s, University of London, Cranmer Terrace, London SWl7 ORE, UK
    Eur J Pharmacol 555:164-73. 2007
    ....
  33. ncbi request reprint Demonstration of functional neuronal beta3-adrenoceptors within the enteric nervous system
    Selim Cellek
    Neurology and Gastrointestinal Centre of Excellence in Drug Discovery, GlaxoSmithKline, Harlow, United Kingdom
    Gastroenterology 133:175-83. 2007
    ..We aimed to investigate the expression of beta(3)-AR in human enteric nervous system and its role in motility and visceral algesia...
  34. ncbi request reprint Identification of genes for the ghrelin and motilin receptors and a novel related gene in fish, and stimulation of intestinal motility in zebrafish (Danio rerio) by ghrelin and motilin
    Catharina Olsson
    Department of Zoophysiology, Goteborg University, Box 463, SE 405 30 Goteborg, Sweden
    Gen Comp Endocrinol 155:217-26. 2008
    ..The results suggest that both ghrelin and motilin can regulate intestinal motility in zebrafish and most likely other teleosts, and are discussed in relation to the evolution of these regulatory peptides...
  35. pmc Neurokinin NK1 and NK3 receptors as targets for drugs to treat gastrointestinal motility disorders and pain
    Gareth J Sanger
    Gastrointestinal Research Department, Neurology Gastroenterology CEDD, GlaxoSmithKline, Harlow, Essex, CM19 5AW, UK
    Br J Pharmacol 141:1303-12. 2004
    ....
  36. ncbi request reprint Effect of a selective and potent central nervous system penetrant, neurokinin-3 receptor antagonist (SB-222200), on cisplatin-induced emesis in the ferret
    Andrew G King
    Department of Microbial, Musculoskeletal, Proliferative Disease Center of Excellence in Drug Discovery AGK, GlaxoSmithKline, Mail Code UP1450, 1250 S Collegeville Road, Collegeville, PA 19426 0989, USA
    Neurosci Lett 376:5-8. 2005
    ..We suggest that if NK-3 receptors are involved in the mechanisms of cisplatin-induced nausea and vomiting, they play only a minor role, relative to the major anti-emetic activity exhibited by 5-HT3 or NK-1 receptor antagonism...
  37. ncbi request reprint Pica--a model of nausea? Species differences in response to cisplatin
    Yong Ling Liu
    Department of Basic Medical Sciences Physiology, St George s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK
    Physiol Behav 85:271-7. 2005
    ....
  38. ncbi request reprint Anti-emetic activity of ghrelin in ferrets exposed to the cytotoxic anti-cancer agent cisplatin
    John A Rudd
    Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
    Neurosci Lett 392:79-83. 2006
    ..05). An ability of ghrelin to reduce emesis is consistent with a role in modulating gastro-intestinal functions and identifies a novel approach to the treatment of emesis...
  39. ncbi request reprint Gastrointestinal neuropharmacology: identification of therapeutic targets
    John B Furness
    Curr Opin Pharmacol 2:609-11. 2002
  40. ncbi request reprint Intrinsic nerve circuits of the gastrointestinal tract: identification of drug targets
    John B Furness
    Department of Anatomy and Cell Biology and Centre for Neuroscience, University of Melbourne, VIC 3010, Parkville, Australia
    Curr Opin Pharmacol 2:612-22. 2002
    ..In the guinea-pig small intestine, where circuits have been most accurately defined, there are 14 functionally identified neuron types, each with a characterised pharmacology of transmission...
  41. ncbi request reprint Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction
    Paul L R Andrews
    Department of Physiology, St George s Hospital Medical School, Cranmer Terrace, SW17 0RE, London, UK
    Curr Opin Pharmacol 2:650-6. 2002
    ..Additional pathophysiological roles for vagal afferents (e.g. in thermoregulation, arousal and fatigue) are being investigated, raising the intriguing possibility of the vagus as a target in non-GI disorders...
  42. pmc Evidence that stimulation of ghrelin receptors in the spinal cord initiates propulsive activity in the colon of the rat
    Yasutake Shimizu
    Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia
    J Physiol 576:329-38. 2006
    ..The pathways through which these responses are generated pass out of the spinal cord via the pelvic nerves and cause propulsive contractions through activation of enteric neurons...
  43. ncbi request reprint Treatment of nausea and vomiting: gaps in our knowledge
    Gareth J Sanger
    Neurology and Gastrointestinal Centre of Excellence in Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, UK
    Auton Neurosci 129:3-16. 2006
    ....
  44. ncbi request reprint Prokineticin-2, motilin, ghrelin and metoclopramide: prokinetic utility in mouse stomach and colon
    Anna K Bassil
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK
    Eur J Pharmacol 524:138-44. 2005
    ..Further, prokineticin-2 and [Nle(13)]-motilin are unlikely to exert gastric prokinetic activity in this species, the inactivity of the latter being consistent with an absence of the motilin receptor in rodents...
  45. doi request reprint Inhibition by tianeptine of neuronally mediated contractions in the rat isolated gastrointestinal tract
    Victoria N Bolton
    ImmunoInflammation CEDD, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG12NY, UK
    Pharmacol Res 57:339-43. 2008
    ..It is not known if the mechanism of this activity is also related in any way to the therapeutic action of tianeptine within the CNS...