Digestive Diseases and Sciences

, Volume 39, Issue 2, pp 321–326 | Cite as

Reciprocal changes in antral gastrin and somatostatin mRNA in pernicious anemia

  • Steven F. Moss
  • Steve Legon
  • John Calam
Originals Articles

Abstract

Somatostatin is involved in the regulation of gastrin by intragastric pH in animal models. To investigate whether this is so in man, we measured gastrin and somatostatin mRNA in endoscopic biopsies from six patients with hypergastrinemia and achlorhydria due to pernicious anemia and 12 age- and sex-matched controls. The pernicious anemia patients had significantly higher fasting plasma gastrin concentrations with a median (range) of 640 (420–3500) pmol/liter compared with 5 (2–58) pmol/liter,P<0.001. The median gastrin mRNA/rRNA ratio was 10.4 (3.7–38.0) in the pernicious anemia patients compared with 1.7 (0.7–8.3) in the controls (P<0.02), and it correlated strongly with the plasma gastrin concentration,r=0.93,P<0.0001. In contrast, the median somatostatin mRNA/rRNA ratio was lower in the pernicious anemia patients 0.84 (0.58–2.32) versus 2.04 (0.05–6.47) in the controls,P<0.05. These findings suggest that in pernicious anemia gastric neutralization leads to hypergastrinemia through the modulation of antral gastrin synthesis by somatostatin.

Key words

achlorhydria pernicious anemia northern blotting gastrins somatostatin messenger RNA 

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References

  1. 1.
    Morson BC, Dawson IMP, Day DW, Jass JR, Price AB, Williams GT: Morson and Dawson's Gastrointestinal Pathology, 3rd ed. London, Blackwell Scientific, 1990Google Scholar
  2. 2.
    Toh B-H, Gleeson PA, Simpson RJ, Moritz RL, Callaghan JM, Goldkorn I, Jones CM, Martinelli TM, Mu F-T, Humphris DC, Pettitt JM, Mori Y, Masuda T, Sobieszczuk P, Weinstock J, Mantamadiotis T, Baldwin GS: The 60 to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a β-subunit of the gastric H+/K+-ATPase (proton pump). Proc Natl Acad Sci USA 87:6418–6422, 1990Google Scholar
  3. 3.
    Weinstein WM: Gastritis.In Gastrointestinal Disease, 4th ed. MH Sleisinger, JS Fordtran (eds). Philadelphia, WB Saunders, 1989, pp 792–813Google Scholar
  4. 4.
    McGuigan JE, Trudeau WL: Serum gastrin concentrations in pernicious anaemia. N Engl J Med 282:358–361, 1970Google Scholar
  5. 5.
    Lanzon-Miller S, Pounder RE, Hamilton MR, Chronos NAF, Ball S, Mercieca JE, Olausson M, Cederberg C: Twenty-four hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer or pernicious anaemia. Aliment Pharmacol Ther 1:225–237, 1987Google Scholar
  6. 6.
    Gustavsson S, Lundquist G: Participation of antral somatostatin in the local regulation of gastrin release. Acta Endocrinol 88:339–346, 1978Google Scholar
  7. 7.
    Schusdziara V, Harris V, Conlon JM, Arimura A, Unger G: Pancreatic and gastric somatostatin release in response to intragastric and intraduodenal nutrients and HCl in the dog. J Clin Invest 62:509–518, 1978Google Scholar
  8. 8.
    Saffouri B, Weir GC, Bitar KN, Makhlouf GM: Gastrin and somatostatin secretion by perfused rat stomach; functional linkage of antral peptides. Am J Physiol 238:G495-G501, 1980Google Scholar
  9. 9.
    McIntosh CHS, Tang CL, Malcolm AJ, Ho M, Kwok YN, Brown JC: Effect of a purified somatostatin monoclonal antibody and its Fab fragment on gastrin release. Am J Physiol 260:G489-G498, 1991Google Scholar
  10. 10.
    Yamada T, Chiba T: Somatostatin.In Handbook of Physiology—The Gastrointestinal System, American Physiological Society, 1989, section 6, vol II. GM Makhlouf (ed.) pp 431–453Google Scholar
  11. 11.
    Brand SJ, Stone D: Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria. J Clin Invest 82:1059–1066, 1988Google Scholar
  12. 12.
    Dockray GJ, Hamer C, Evans D, Varro A, Dimaline D: The secretory kinetics of the G-cell in omeprazole treated rats. Gastroenterology 100:1187–1194, 1991Google Scholar
  13. 13.
    McNulty CAM, Dent JC, Uff JS, Gear MWL, Wilkinson SP: Detection ofCampylobacter pylori by the biopsy urease test: an assessment in 1445 patients. Gut 30:1058–1062, 1989Google Scholar
  14. 14.
    Bryant MG, Adrian TE: Gastrin.In Radioimmunoassay of Gut Regulatory Peptides. SR Bloom, RG Long (eds). London, WB Saunders, 1982, pp 51–59Google Scholar
  15. 15.
    Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate phenol-chloroform extraction. Anal Biochem 162:156–159, 1987Google Scholar
  16. 16.
    Ito R, Sato K, Helmer T, Jay G, Agarwal K: Structural analysis of the gene encoding gastrin: The large intron contains anAlu sequence. Proc Natl Acad Sci USA 81:4662–4666, 1984Google Scholar
  17. 17.
    Shen LP, Pictet RL, Rutter WJ: Human somatostatin I: Sequence of the cDNA. Proc Natl Acad Sci USA 79:4575–4579, 1982Google Scholar
  18. 18.
    Feinberg AP, Vogelstein BA: A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13, 1983Google Scholar
  19. 19.
    Holst JJ, Jensen SL, Knuhtsen S, Nielsen OV, Rehfeld JF: Effect of vagus, gastric inhibitory polypeptide, and HCl on gastrin and somatostatin release from perfused pig antrum. Am J Physiol 244:G515-G522, 1983Google Scholar
  20. 20.
    Wu V, Sumii K, Tari A, Sumii M, Walsh JH: Regulation of rat antral gastrin and somatostatin gene expression during starvation and after refeeding. Gastroenterology 101:1552–1558, 1991Google Scholar
  21. 21.
    Karnik PS, Monahan SJ, Wolfe MM: Inhibition of gastrin gene expression by somatostatin. J Clin Invest 83:367–372, 1989Google Scholar
  22. 22.
    Bachwich D, Merchant J, Brand SJ: Identification of acis-regulatory element mediating somatostatin inhibition of epidermal growth factor-stimulated gastrin gene transcription. Mol Endocrinol 6:1175–1184, 1992Google Scholar
  23. 23.
    Dimaline R, Evans D, Varro A, Dockray GJ: Reversal by omeprazole of the depression of gastrin-cell function by fasting in the rat. J Physiol 433:483–493, 1991Google Scholar
  24. 24.
    Arnold R, Hulst MV, Neuhof CH, Schwarting H, Becker HD, Creutzfeldt W: Antral gastrin-producing G-cells and somatostatin-producing D-cells in different states of acid secretion. Gut 23:285–291, 1982Google Scholar
  25. 25.
    Moss S, Calam J:Helicobacter pylori and peptic ulcers: The present position. Gut 33:289–292, 1992Google Scholar
  26. 26.
    Moss SF, Legon S, Bishop AE, Polak JM, Calam J: Effect ofHelicobacter pylori on gastric somatostatin in duodenal ulcer disease. Lancet 340:930–932, 1992Google Scholar
  27. 27.
    Fong TL, Dooley CP, Dehesa M, Cohen H, Carmel R, Fitzgibbons PL, Perez-Perez GI, Blaser MJ:Helicobacter pylori infection in pernicious anaemia: A prospective controlled study. Gastroenterology 100:328–332, 1991Google Scholar
  28. 28.
    Deprez PH, Ghosh P, Goodlad RA, Lacey SL, Millership S, Playford RJ, Lee CY, Calam J: Hypergastrinaemia: A new mechanism. Lancet 338:410–411, 1991Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Steven F. Moss
    • 1
  • Steve Legon
    • 1
  • John Calam
    • 1
  1. 1.From the Departments of Gastroenterology and Chemical Pathology, Royal Postgraduate Medical SchoolHammersmith HospitalLondonUK

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