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  • Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist

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Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist
  1. P Hildebranda,
  2. F S Lehmanna,
  3. S Ketterera,
  4. A D Christa,
  5. T Stingelina,
  6. J Beltingera,
  7. A H Gibbonsd,
  8. D H Coyb,
  9. J Calamd,
  10. F Larsenc,
  11. C Beglingera
  1. aDivision of Gastroenterology and Department of Research, University Hospital, CH-4031 Basel, Switzerland, bDepartment of Medicine, Peptide Research Laboratories, Tulane University Medical Center, New Orleans, LA 70112, USA, cIpsen International Ltd, London W8 5HH, UK, dDivision of Medicine, Medicine A, Hammersmith Hospital, London W12 0NN, UK
  1. Professor C Beglinger.beglinger{at}tuir.ch

Abstract

BACKGROUND AND AIMS The main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to determine if endogenous GRP is a physiological regulator of gastric acid secretion and gastrin release.

METHODS Our study consisted of three parts. In part I, subjects received saline or BIM26226 followed by graded doses of intravenous human GRP in a four period crossover design. In part II, subjects received BIM26226 or saline during oral meal ingestion or modified sham feeding. In part III, subjects received an acidified meal in the presence and absence of BIM26226 in a two period crossover design. In addition, gastrin and somatostatin mRNA were measured in biopsy specimens during saline and BIM26226 infusion.

RESULTS BIM26226 dose dependently inhibited GRP induced acid output. Acid secretion after oral liquid meal intake and sham feeding was significantly inhibited by BIM26226 (p<0.01) whereas plasma gastrin release remained unchanged. Gastrin and somatostatin mRNAs were not significantly different after saline or BIM26226.

CONCLUSIONS BIM26226 is a potent GRP antagonist in humans. Endogenous GRP may be a physiological regulator of gastric acid secretion. Gastrin release does not seem to be under the control of GRP.

  • gastrin
  • gastric acid secretion
  • gastrin releasing peptide
  • gastric function
  • BIM26226

  • Abbreviations used in this paper

    GRP
    gastrin releasing peptide
    PEG
    polyethylene glycol
    CCK
    cholecystokinin
    GAPDH
    glyceraldehyde phosphate dehydrogenase
    NMB
    neuromedin B
    ECL
    enterochromaffin-like

    • https://doi.org/10.1136/gut.49.1.23

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    • Abbreviations used in this paper

      GRP
      gastrin releasing peptide
      PEG
      polyethylene glycol
      CCK
      cholecystokinin
      GAPDH
      glyceraldehyde phosphate dehydrogenase
      NMB
      neuromedin B
      ECL
      enterochromaffin-like
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