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The gastric H, K ATPase

  • Chapter
Proton Pump Inhibitors

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

Abstract

On 11 December 1823, at the Royal Society, William Prout presented his landmark paper “On the Nature of Acid and Saline Matters Usually Existing in the Stomach of Animals”. This presentation was unique in two ways. First, Prout had specifically identified hydrochloric acid in the gastric juice of many species (man, dog, rabbit, horse, calf and hare), and second, he was able to quantify the free and total hydrochloric acid and chloride present. The acid was measured by neutralization with potash solution of known strength and the chloride by titration with silver nitrate. He also proposed that chloride may be secreted from blood to lumen by electrical means and that, when gastric acid was secreted, the blood would become alkaline (now recognized as the postprandial alkaline tide). More than 100 years were to elapse before his subsequent proposal was confirmed.

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References

  1. Forte JG, Ganser A, Beesley R, Forte TM (1975) Unique enzymes of purified microsomes from pig fundic mucosa. Gastroenterology 69: 175–189

    PubMed  CAS  Google Scholar 

  2. Lee J, Simpson G, Scholes P (1974) An ATPase from dog gastric mucosa: changes of outer pH in suspensions of dog membrane vesicles accompanying ATP hydrolysis. Biochem Biophys Res Commun 60: 825–832

    Article  PubMed  CAS  Google Scholar 

  3. Sachs G, Chang HH, Rabon E, Schackman R, Lewin M, Saccomani G (1976) A nonelectrogenic H+ pump in plasma membranes of hog stomach. J Biol Chem 251: 7690–7698

    PubMed  CAS  Google Scholar 

  4. Berglind T, Dibona DR, Pace CS, Sachs GG (1980) ATP dependence of hydrogen ion secretion. J Cell Biol 85: 392–401

    Article  Google Scholar 

  5. Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjöstrand SE, Wallmark B (1981) Substituted benzimidazoles inhibit gastric acid secretion by blocking (H++K+)ATPase. Nature 290: 159–161

    Article  PubMed  CAS  Google Scholar 

  6. Wallmark B, Larsson H, Humble L (1985) The relationship between gastric acid secretion and gastric H+, K+-ATPase activity. J Biol Chem 260: 13681–13684

    PubMed  CAS  Google Scholar 

  7. Glynn IM, Karlish SJ (1990) Occluded ions in active transport. Ann Rev Biochem 59: 171

    Article  PubMed  CAS  Google Scholar 

  8. Walderhaug, MO, Post RL, Saccomani G, Leonard RT, Briskin DP (1985) Structural relatedness of three ion-transport adenosine triphosphatases around their active sites of phosphorylation. J Biol Chem 260: 3852–3859

    PubMed  CAS  Google Scholar 

  9. Melchers K, Weitzenegger T, Bufimann A, Steinhilber W, Sachs G, Schafer KP (1996) Cloning and membrane topology of a P type ATPase from Helicobacter pylori. J Biol Chem 271: 446–457

    Article  PubMed  CAS  Google Scholar 

  10. Smith DL, Tao T, Maguire ME (1993) Membrane topology of a P-type ATPase. The MgtB magnesium transport protein of Salmonella typhimurium. J Biol Chem 268: 22469–22479

    PubMed  CAS  Google Scholar 

  11. Lutsenko S, Kaplan JH (1995) Organization of P-type ATPases: significance of structural diversity. Biochemistry 34:15607–15613

    Article  PubMed  CAS  Google Scholar 

  12. Rabon EC, Reuben MA (1990) The mechanism and structure of the gastric H, K-ATPase. Ann Rev Physiol 52: 321–344

    Article  CAS  Google Scholar 

  13. Shull GE (1990) cDNA cloning of the beta-subunit of the rat gastric H, H,, K-ATPase. J Biol Chem 265: 12123–12126

    PubMed  CAS  Google Scholar 

  14. Shull GE, Lingrel JB (1986) Molecular cloning of the rat stomach (H+ + K+)-ATPase. J Biol Chem 261: 16788–16791

    PubMed  CAS  Google Scholar 

  15. Reuben MA, Lasater LS, Sachs G (1990) Characterization of a beta subunit of the gastric H+/K(+)-transpoting ATPase. Prvc Natl Acad Sci USA 87: 6767–6771

    Article  CAS  Google Scholar 

  16. Post RL (1974) A reminiscence about sodium, potassium-ATPase. Ann N Y Acad Sci 242:6–11

    Article  PubMed  CAS  Google Scholar 

  17. MacLennan DH, Brandi CJ, Coreczak B, Green NM (1985) Amino acid sequence of the Ca2+ Mg2+ dependent ATPase from rabbit muscle sarcoplasmic reticulum, deduced from its complementary DNA sequence. Nature 316: 696–700

    Article  PubMed  CAS  Google Scholar 

  18. Maeda M, Ishizaki J, Futai M (1988) cDNA cloning and sequence determination of pig gastric (H+ + K+)-ATPase. Biochem Biophys Res Commun 157: 203–209

    Article  PubMed  CAS  Google Scholar 

  19. Stewart B, Wallmark B, Sachs G (1981) The interaction of H+ and K+ with the partial reactions of gastric H, H,,K-ATPase. J Biol Chem 256: 2682–2690

    PubMed  CAS  Google Scholar 

  20. Rabon EC, Smillie K, Seru V, Rabon R (1993) Rubidium occlusion within tryptic peptides of the H, K-ATPase. J Biol Chem 268: 8012–8018

    PubMed  CAS  Google Scholar 

  21. Lorentzon P, Sachs G, Wallmark B (1988) Inhibitory effects of cations on the gastric H+,K+-ATPase. A potential-sensitive step in the K+ limb of the pump cycle. J Biol Chem 263: 10705–10710

    PubMed  CAS  Google Scholar 

  22. Wallmark B, Stewart HB, Rabon E, Saccomani G, Sachs G (1980) The catalytic cycle of gastric (H+ + K+)-ATPase. J Biol Chem 255: 5313–5319

    PubMed  CAS  Google Scholar 

  23. Rabon EC, McFall TL, Sachs G (1982) The gastric [H,K]ATPase: H+/ATP stoichiometry. J Biol Chem 257: 6296–6299

    PubMed  CAS  Google Scholar 

  24. Helander HF, Hirschowitz BI (1972) Quantitative ultrastructural studies on gastric parietal cells. Gastroenterology 63:951–961

    PubMed  CAS  Google Scholar 

  25. Gibert AJ, Hersey SJ (1982) Morphometric analysis of parietal cell membrane transformations in isolated gastric glands. J Membr Biol 67: 113–124

    Article  PubMed  CAS  Google Scholar 

  26. Forte TM, Machen TE, Forte JG (1977) Ultrastructural changes in oxyntic cells associated with secretory function. A membrane recycling hypothesis. Gastroenterology 73: 941

    PubMed  CAS  Google Scholar 

  27. Wolosin JM, Forte JG (1984) Stimulation of oxyntic cell triggers K+ and C1- conductances in apical H+-K+-ATPase membrane. Am J Physiol 246: C537–C545

    PubMed  CAS  Google Scholar 

  28. Sachs G, Zeng N, Prinz C (1997) Physiology of isolated gastric endocrine cells. Ann Rev Physiol 59:243–256

    Article  CAS  Google Scholar 

  29. Im WB, Blakeman DP, Davis JP (1985) Irreversible inactivation of rat gastric (H+-K+)-ATPase in vivo by omeparzole. Biochem Biophys Res Commun 126: 78–82

    Article  PubMed  CAS  Google Scholar 

  30. Wallmark B, Larsson H, Humble L (1985) The relationship between gastric acid secretion and gastric H+,K+-ATPase activity. J Biol Chem 260: 13681–13684

    PubMed  CAS  Google Scholar 

  31. Gedda K, Scott D, Besancon M et al (1995) Turnover of the gastric H+,K+-ATPase α subunit and its effect on inhibition of gastric acid secretion. Gastroenterology 109: 1134–1141

    Article  PubMed  CAS  Google Scholar 

  32. Maeda M, Tagaya M, Futai M (1988) Modification of gastric (H+ + K+)-ATPase with pyridoxal 5′-phosphate. J Biol Chem 263: 3652–3656

    PubMed  CAS  Google Scholar 

  33. Xu K-Y (1989) Any of several lysines can react with 5′-isothiocyanatofluorescein to inactivate sodium and potassium ion activated adenosine triphosphatase. Biochemistry 28: 5764–5772

    Article  PubMed  CAS  Google Scholar 

  34. Besancon M, Shin JM, Mercier F, Munson K, Miller M, Hersey S, Sachs G (1993) Membrane topology and omeprazole labeling of the gastric H,K-adenosinetriphosphatase. Biochemistry 32: 2345–2355

    Article  PubMed  CAS  Google Scholar 

  35. Bamberg K, Sachs G (1994) Topological analysis of the HK ATPase using in vitro translation. J Biol Chem 269: 16909–16919

    PubMed  CAS  Google Scholar 

  36. Munson KB, Gutierrez C, Balaji VN, Ramnarayan K, Sachs G (1991) Identification of an extracytoplasmic region of H+,K+-ATPase labeled by a K+-competitive photoaffinity inhibitor. J Biol Chem 266: 18976–18988

    PubMed  CAS  Google Scholar 

  37. Jewell EA, Lingrel JB (1993) Site-directed mutagenesis of the Na, K-ATPase. Consequences of the substitutions of negatively charged amino acids localized in the transmembrane domains. Biochem 32: 13523–13530

    Article  Google Scholar 

  38. Swarts HG, Klaassen CH, de Boer M, Fransen JA, De Pont JJ (1996) Role of negatively charged residues in the fifth and sixth transmembrane domains of the catalytic subunit of gastric H+,K+-ATPase. J Biol Chem 271: 29764–29772

    Article  PubMed  CAS  Google Scholar 

  39. Rabon E, Sachs G, Bassilian S, Leach C, Keeling D (1991) A K+-competitive fluorescent inhibitor of the H, H,, K-ATPase. J Biol Chem 266: 12395–12401

    PubMed  CAS  Google Scholar 

  40. Sachs G, Shin JM, Besancon M, Prinz C (1993) The continuing development of gastric acid pump inhibitors (lansoprazole). Aliment Pharmacol Ther 7 (Suppl 1): 4–12

    PubMed  CAS  Google Scholar 

  41. Besancon M, Simon A, Sachs G, Shin JM (1997) Sites of reaction of the gastric H,K-ATPase with extracytoplsmic thiol reagents. J Biol Chem 272: 22438–22446

    Article  PubMed  CAS  Google Scholar 

  42. Bamberg K, Sachs G (1994) Topological analysis of the HK ATPase using in vitro translation. J Biol Chem 269: 16909–16919

    PubMed  CAS  Google Scholar 

  43. Hall K, Perez G, Mayer P, Gutierrez C, Munson K, Hersey, SJ, Kaplan JH, Sachs G (1990) Location of the carbohydrates present in the HK-ATPase vesicles isolated from hog gastric mucosa. Biochemistry 29: 701–706

    Article  PubMed  CAS  Google Scholar 

  44. Lemas MV, Hamrich M, Takeyasu K, Fambrough DM (1994) 26 Amino acids of an extracellular domain of the Na,K-ATPase alpha-subunit are sufficient for assembly with the Na,K-ATPase beta-subunit. J Biol Chem 269: 8255–8259

    PubMed  CAS  Google Scholar 

  45. Beggah AT, Beguin P, Jaunin P, Peittshc MC, Geering K (1993) Hydrophobic C terminal amino acids in the β subunit are involved in assembly with the a subunit of Na,K ATPase. Biochemistry 32: 14117–14124

    Article  PubMed  CAS  Google Scholar 

  46. Horisberger JD, Jaunin P, Reuben MA, Lasater LS, Chow DC, Forte JG, Sachs G, Rossier BC, Geering K (1991) The H,K-ATPase beta-subunit can act as a surrogate for the betasubunit of Na,K-pumps. J Biol Chem 266: 19131–19134

    PubMed  CAS  Google Scholar 

  47. Gottardi CJ, Caplan MJ (1993) Molecular requirements for the cell-surface expression of multisubunit ion-transporting ATPases. J Biol Chem 268: 14342–14347

    PubMed  CAS  Google Scholar 

  48. Shin JM, Sachs G (1996) Identification of a region of the H,K ATPase alpha subunit associated with the beta subunit. J Biol Chem 269: 8642–8646

    Google Scholar 

  49. Melle-Milovanovic D, Milovanovic M, Nagpal S, Sachs G, Shin JM (1998) Regions of association between the alpha and the beta subunit of the gastric H, H,,K-ATPase. J Biol Chem 273: 11075–11081

    Article  PubMed  CAS  Google Scholar 

  50. Polvani C, Sachs G, Biostein R (1989) Sodium ions as substitutes for protons in the gastric H+K+-ATPase. J Biol Chem 264: 17854

    PubMed  CAS  Google Scholar 

  51. Lutsenko S, Anderko R, Kaplan JH (1995) Membrane disposition of the M5-M6 hairpin of Na+,K(+)-ATPase alpha subunit is ligand dependent. Proc Natl Acad Sci USA 92(17): 7936–7940

    Article  PubMed  CAS  Google Scholar 

  52. Palasis M, Kuntzweiler TA, Arguello JM, Lingrel JB (1996) Ouabain interactions with the H5-H6 hairpin of the Na,K-ATPase reveal a possible inhibition mechanism via the cation binding domain. J Biol Chem 271: 14176–14182

    Article  PubMed  CAS  Google Scholar 

  53. Beguin P, Geering K (1997) Structural domain implication in ER degradation of alpha subunit of Na,K-ATPase. Ann N Y Acad Sci 834: 540–542

    Article  PubMed  CAS  Google Scholar 

  54. Lyu RM, Farley RA (1977) Amino acids Val 115-Ile 126 of rat gastric H(+)-K(+)-ATPase confer high affinity for SCH-28080 to (Na(+)-(K+)-ATPase. Am J Physiol 272: C1717–1725

    Google Scholar 

  55. Zhang P, Toyoshima C, Yonekra K, Green NM, Stokes DL (1998) Structure of the calcium pump from sarcoplasmic reticulum at 8A resolution. Nature 992: 835–839

    Google Scholar 

  56. Auer M, Scarbrough GA, Kuhlbrandt W (1998) Three dimensional map of the plasma membrane H+ ATPase in the open conformation. Nature 392: 840–843

    Article  PubMed  CAS  Google Scholar 

  57. Feng J, Lingrel JB (1994) Analysis of amino acid residues in the H5-H6 transmembrane and extracellular domains of Na,K-ATPase alpha subunit identifies threonine 797 as a determinant of ouabain sensitivity. Biochemistry 33: 4218–4224

    Article  PubMed  CAS  Google Scholar 

  58. Clarke DM, Loo TW, MacLennan DM (1990) Functional consequences of alterations to polar amino acids located in the transmembrane domain of the Ca-ATPase of the sarcoplasmic reticulum. J Biol Chem, 265: 6262–6267

    PubMed  CAS  Google Scholar 

  59. Saccomani G, Crago S, Mihas A, Dailey DW, Sachs G (1978) Tissue and cell localization of hog gastrin plasma membrane by antibody techniques. Acta Physiol Scand Suppl: 1978:293–305

    Google Scholar 

  60. Alderuccio F, Gleeson PA, Berzins SP, Martin M, Van Driel IR (1997) Toh BH Expression of the gastric H/K-ATPase alpha-subunit in the thymus may explain the dominant role of the beta-subunit in the pathogenesis of autoimmune gastritis. Autoimmunity 25: 167–175

    Article  PubMed  CAS  Google Scholar 

  61. Wallmark B, Sachs G, Mardh S, Fellenius E (1983) Inhibition of gastric hydrogen potassium ATPase by the substituted benzimidazole, picroprazole. Biochim Biophys Acta 728: 31–38

    Article  PubMed  CAS  Google Scholar 

  62. Brandstrom A, Lindberg P, Bergman N-A, Alminger T, Ankner K, Junggren U, Lamm B, Nordberg P, Erickson M, Grundevik I et al (1989) Chemical reactions of omeprazole and omeprazole analogues. I. A survey of the chemical transformations of omeprazole and its analogues. Acta Chem Scand 43: 536–611

    Article  Google Scholar 

  63. Im WB, Blakeman DP, Mendlein J, Sachs G (1984) Inhibition of proton potassium ATPase and proton accumulation in hog gastric membranes by trifluoperaz, verapamil and 8 N,N-diethylaminooctyl-3,4-5-trimethoxybenzoate. Biochim Biophys Acta 770: 65–75

    Article  PubMed  CAS  Google Scholar 

  64. Wallmark B, Briving C, Fryklund J, Munson K, Jackson R, Mendlein J, Rabon E, Sachs G (1987) Inhibition of gastric H+,K+-ATPase and acid secretion by SCH 28080, a substituted pyridyl(1, 2a)imidazole. J Biol Chem 262: 2077–2084

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine and Physiology, UCLA and Wadsworth VA Hospital, Los Angeles, USA

    George Sachs & Björn Wallmark

  2. ASTRA-Hässle, Göteborg, Sweden

    George Sachs & Björn Wallmark

Authors
  1. George Sachs
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  2. Björn Wallmark
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Editor information

Editors and Affiliations

  1. Centre for Gastroenterological Research, University of Göteborg, S-41345, Göteborg, Sweden

    Lars Olbe

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© 1999 Springer Basel AG

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Sachs, G., Wallmark, B. (1999). The gastric H, K ATPase. In: Olbe, L. (eds) Proton Pump Inhibitors. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8795-3_2

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  • DOI: https://doi.org/10.1007/978-3-0348-8795-3_2

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9777-8

  • Online ISBN: 978-3-0348-8795-3

  • eBook Packages: Springer Book Archive

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