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Biochemistry of Gastric Acid Secretion: H+‐K+‐ATPase

G. Sachs, J. Kaunitz, J. Mendlein, B. Wallmark

10.1002/cphy.cp060312

Source: Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Parietal Cell Acid Secretion and H+‐K+‐ATPASE
2 General Aspects of H+‐K+‐ATPASE
3 Structure of H+‐K+‐ATPASE
3.1 Sequence
3.2 Protein Composition
3.3 Dimensions
4 Transport by H+‐K+‐ATPASE
4.1 Resting Vesicles
4.2 Stimulated Vesicles
4.3 Transport Modes of H+‐K+‐ATPase
4.4 H+‐K+‐ATPase in Parietal Cell
5 Kinetics of H+‐K+‐ATPASE
5.1 Steady‐State Kinetics of ATPase
5.2 Steady‐State Kinetics of Phosphatase Reaction
5.3 Phosphorylation from ATP
5.4 ATP‐ADP Exchange
5.5 Potassium‐Dependent Dephosphorylation
5.6 Phosphorylation from Pi
6 Conformations of H+‐K+‐ATPASE
6.1 Tryptic Digestion
6.2 Fluorescence
7 Inhibition of H+‐K+‐ATPASE
7.1 Site‐Specific Inhibitors
7.2 Group‐Selective Reagents
8 Biosynthesis of H+‐K+‐ATPASE
9 Tissue Distribution of H+‐K+‐ATPASE
10 Model for H+‐K+‐ATPASE
Figure 1. Figure 1.

Amino acid sequence of rat H+‐K+‐ATPase as deduced by cDNA cloning methods. An additional translatable region that could code for a peptide of ∼40 amino acids is shown below the sequence for the catalytic subunit. Whether it is synthesized or its function is unknown, so far this structure is unique for the E1, E2 cDNA sequences.
Figure 2. Figure 2.

Model of the secondary structure of the H+‐K+‐ATPase catalytic subunit, where various symbols denote predictions for α‐helix, β‐sheet, and β‐turns. If no discrimination between α and β is statistically significant, a separate symbol is used. Probabilities used depend on known structures for soluble proteins and may not apply to membrane‐embedded molecules 162. FITC, fluorescein isothiocyanate.
Figure 3. Figure 3.

Composite illustrating various structural features of hog gastric vesicle, which contains the H+‐K+‐ATPase. A: tannic acid‐glutaraldehyde‐fixed section of vesicles prepared by centrifugation and free‐flow electrophoresis. B: freeze‐fracture image of gastric vesicles showing membrane‐embedded region. C: reconstruction of an optical diffraction pattern of 2‐dimensional crystals of the H+‐K+‐ATPase. D: model of outline of the H+‐K+‐ATPase determined from dimensions calculated from A, B, and C.

From Sachs 127a)
Figure 4. Figure 4.

ATPase activity of hog gastric vesicles that are first loaded with 150 mM KCl diluted 10‐fold with choline Cl‐, and then Mg2+ATP is added. Burst of K+‐ATPase activity is observed, followed by a return to base‐line (K+‐independent) ATP hydrolysis (lower curve). This shows that internal (luminal) K+ is required for K+ stimulation of ATPase activity and that K+ is exported during the enzyme reaction. Calculation gives a K+/ATP stoichiometry = 2. Inset: ATPase activity of this preparation in unequilibrated vesicles, with K+, K+ + valinomycin (Val), and K+ + nigericin (Nig).
Figure 5. Figure 5.

A: pH metric study of proton transport by hog gastric vesicles. Vesicles were loaded in 150 mM KCl for the indicated times, and pH‐gradient formation was initiated by addition of Mg2+‐ATP in a 5 mM glycylglycine buffer at pH 6.12. Gradient formation was monitored by alkalinization of the medium using a pH electrode. B: osmotic sensitivity of the pH gradient formed after KCl loading for different times, showing that there is a progressive loss of osmotic sensitivity, as KCl is present before the addition of Mg2+‐ATP. TCS, tetrachlorosalicylanilide; val, valinomycin.
Figure 6. Figure 6.

H+‐ to ATP‐transport stoichiometry, measured at a medium pH of 6.12, in vesicles that were preequilibrated with KCl. Ionophore‐independent ATPase activity was subtracted, because this reflects transport‐incompetent enzyme activity. H+‐transport rate and ATPase rates were initial rates measured at various ATP concentrations. Ratio of 2 H+/ATP is obtained, ○, H+; •, Pi.
Figure 7. Figure 7.

A: comparison of H+ transport in rabbit microsomes derived from an animal treated with cimetidine (resting, left trace) or from an animal treated with histamine (right trace), showing that when the vesicles were derived from a stimulated stomach, neither KCl preincubation nor ionophore was necessary for ATP‐dependent H+ transport. B: flux measurements of conductance in stimulated rabbit vesicles. Vesicles were loaded with KCl, external medium was removed, and vesicles were placed in a medium containing only 86Rb+. Uptake of 86Rb+ depends on the presence of the exchange‐only mode of the H+‐K+‐ATPase and is inhibited by SCH 28080, a K+‐competitive antagonist of this enzyme, and on the presence of a conductance pathway where 86Rb+ uptake is driven by the K+ diffusion potential across this conductance and is inhibited by the electrogenic protonophore tetra‐chlorosalicylanilide (TCS). TMACl, tetramethylammonium chloride.
Figure 8. Figure 8.

Conceptual model of the H+‐K+‐ATPase in a membrane derived from resting (upper) and stimulated (lower) stomach. In resting membranes, valinomycin is shown as providing a KCl pathway to allow K+ access to the luminal face of the pump, whereas in the stimulated state the membrane contains K+ and Cl‐ conductances that allow the penetration of KCl.

From Sachs 127a)
Figure 9. Figure 9.

Use of 14CO2 production to demonstrate stimulation of acid secretion in cimetidine‐treated rabbit gastric glands by histamine and dibutyryl cAMP (db cAMP), as well as to show the basal CO2 production when the H+‐K+‐ATPase is inhibited by the pump blocker, omeprazole.
Figure 10. Figure 10.

Ion pathways that have been described in stimulated oxyntic cell and are related to acid secretion. Basal‐lateral membrane contains the H+‐K+‐ATPase, Na+‐H+ and HCO3‐‐Cl‐ exchange pathways, and cAMP‐ and [Ca2+]i‐activatable K+ conductances. Canalicular membrane contains the H+‐K+‐ATPase and K+ and Cl‐ conductances demonstrated in vesicle studies.
Figure 11. Figure 11.

Barrier‐site model for the H+‐K+‐ATPase, showing the necessity for alteration of barriers in the transmembrane path, as well as the change in affinity for transported ions. Conformation where ion‐binding sites face the cytosol defines the E1 state and where ion‐binding sites face the lumen defines the E2 state of this class of enzyme.
Figure 12. Figure 12.

Biphasic effect of ATP concentration on H+‐K+‐ATPase activity, where at each ATP concentration the level of K+ was set to give maximal activity. Data translate into a high and low apparent Km, with maximal activity found with binding of ATP to the low‐affinity state of the enzyme. ○, +K+; •, ‐K+.
Figure 13. Figure 13.

Schematic of the sequence of reactions that have been shown for the H+‐K+‐ATPase, including the interaction of the enzyme with the K+‐competitive inhibitor SCH 28080. Reactions are written as reversible, but backreaction from E2‐P to E1‐ has not been shown.

From Sachs 127a)
Figure 14. Figure 14.

A: formula of SCH 28080 in the active, protonated form with charge distribution shown. B: reactive cycle of omeprazole after protonation of the prodrug. Initial protonation on benzimidazole nitrogen is followed by slow rearrangement to the spirocompound, which then rapidly forms either the sulfenamide (the major reactive species) or the sulfenic acid, both of which are cationic SH reagents.
Figure 15. Figure 15.

Conceptual model of E1‐E2‐type pump, where coupling between scalar ATP hydrolysis and vectorial ion transport is due to a mobile sector of the pump that inserts partway into the hydrophobic domain. Thus these pumps act as liner mechanochemical devices, and conformations analyzed by different means are represented by different locations of mobile pump sector.


Figure 1.

Amino acid sequence of rat H+‐K+‐ATPase as deduced by cDNA cloning methods. An additional translatable region that could code for a peptide of ∼40 amino acids is shown below the sequence for the catalytic subunit. Whether it is synthesized or its function is unknown, so far this structure is unique for the E1, E2 cDNA sequences.



Figure 2.

Model of the secondary structure of the H+‐K+‐ATPase catalytic subunit, where various symbols denote predictions for α‐helix, β‐sheet, and β‐turns. If no discrimination between α and β is statistically significant, a separate symbol is used. Probabilities used depend on known structures for soluble proteins and may not apply to membrane‐embedded molecules 162. FITC, fluorescein isothiocyanate.



Figure 3.

Composite illustrating various structural features of hog gastric vesicle, which contains the H+‐K+‐ATPase. A: tannic acid‐glutaraldehyde‐fixed section of vesicles prepared by centrifugation and free‐flow electrophoresis. B: freeze‐fracture image of gastric vesicles showing membrane‐embedded region. C: reconstruction of an optical diffraction pattern of 2‐dimensional crystals of the H+‐K+‐ATPase. D: model of outline of the H+‐K+‐ATPase determined from dimensions calculated from A, B, and C.

From Sachs 127a)


Figure 4.

ATPase activity of hog gastric vesicles that are first loaded with 150 mM KCl diluted 10‐fold with choline Cl‐, and then Mg2+ATP is added. Burst of K+‐ATPase activity is observed, followed by a return to base‐line (K+‐independent) ATP hydrolysis (lower curve). This shows that internal (luminal) K+ is required for K+ stimulation of ATPase activity and that K+ is exported during the enzyme reaction. Calculation gives a K+/ATP stoichiometry = 2. Inset: ATPase activity of this preparation in unequilibrated vesicles, with K+, K+ + valinomycin (Val), and K+ + nigericin (Nig).



Figure 5.

A: pH metric study of proton transport by hog gastric vesicles. Vesicles were loaded in 150 mM KCl for the indicated times, and pH‐gradient formation was initiated by addition of Mg2+‐ATP in a 5 mM glycylglycine buffer at pH 6.12. Gradient formation was monitored by alkalinization of the medium using a pH electrode. B: osmotic sensitivity of the pH gradient formed after KCl loading for different times, showing that there is a progressive loss of osmotic sensitivity, as KCl is present before the addition of Mg2+‐ATP. TCS, tetrachlorosalicylanilide; val, valinomycin.



Figure 6.

H+‐ to ATP‐transport stoichiometry, measured at a medium pH of 6.12, in vesicles that were preequilibrated with KCl. Ionophore‐independent ATPase activity was subtracted, because this reflects transport‐incompetent enzyme activity. H+‐transport rate and ATPase rates were initial rates measured at various ATP concentrations. Ratio of 2 H+/ATP is obtained, ○, H+; •, Pi.



Figure 7.

A: comparison of H+ transport in rabbit microsomes derived from an animal treated with cimetidine (resting, left trace) or from an animal treated with histamine (right trace), showing that when the vesicles were derived from a stimulated stomach, neither KCl preincubation nor ionophore was necessary for ATP‐dependent H+ transport. B: flux measurements of conductance in stimulated rabbit vesicles. Vesicles were loaded with KCl, external medium was removed, and vesicles were placed in a medium containing only 86Rb+. Uptake of 86Rb+ depends on the presence of the exchange‐only mode of the H+‐K+‐ATPase and is inhibited by SCH 28080, a K+‐competitive antagonist of this enzyme, and on the presence of a conductance pathway where 86Rb+ uptake is driven by the K+ diffusion potential across this conductance and is inhibited by the electrogenic protonophore tetra‐chlorosalicylanilide (TCS). TMACl, tetramethylammonium chloride.



Figure 8.

Conceptual model of the H+‐K+‐ATPase in a membrane derived from resting (upper) and stimulated (lower) stomach. In resting membranes, valinomycin is shown as providing a KCl pathway to allow K+ access to the luminal face of the pump, whereas in the stimulated state the membrane contains K+ and Cl‐ conductances that allow the penetration of KCl.

From Sachs 127a)


Figure 9.

Use of 14CO2 production to demonstrate stimulation of acid secretion in cimetidine‐treated rabbit gastric glands by histamine and dibutyryl cAMP (db cAMP), as well as to show the basal CO2 production when the H+‐K+‐ATPase is inhibited by the pump blocker, omeprazole.



Figure 10.

Ion pathways that have been described in stimulated oxyntic cell and are related to acid secretion. Basal‐lateral membrane contains the H+‐K+‐ATPase, Na+‐H+ and HCO3‐‐Cl‐ exchange pathways, and cAMP‐ and [Ca2+]i‐activatable K+ conductances. Canalicular membrane contains the H+‐K+‐ATPase and K+ and Cl‐ conductances demonstrated in vesicle studies.



Figure 11.

Barrier‐site model for the H+‐K+‐ATPase, showing the necessity for alteration of barriers in the transmembrane path, as well as the change in affinity for transported ions. Conformation where ion‐binding sites face the cytosol defines the E1 state and where ion‐binding sites face the lumen defines the E2 state of this class of enzyme.



Figure 12.

Biphasic effect of ATP concentration on H+‐K+‐ATPase activity, where at each ATP concentration the level of K+ was set to give maximal activity. Data translate into a high and low apparent Km, with maximal activity found with binding of ATP to the low‐affinity state of the enzyme. ○, +K+; •, ‐K+.



Figure 13.

Schematic of the sequence of reactions that have been shown for the H+‐K+‐ATPase, including the interaction of the enzyme with the K+‐competitive inhibitor SCH 28080. Reactions are written as reversible, but backreaction from E2‐P to E1‐ has not been shown.

From Sachs 127a)


Figure 14.

A: formula of SCH 28080 in the active, protonated form with charge distribution shown. B: reactive cycle of omeprazole after protonation of the prodrug. Initial protonation on benzimidazole nitrogen is followed by slow rearrangement to the spirocompound, which then rapidly forms either the sulfenamide (the major reactive species) or the sulfenic acid, both of which are cationic SH reagents.



Figure 15.

Conceptual model of E1‐E2‐type pump, where coupling between scalar ATP hydrolysis and vectorial ion transport is due to a mobile sector of the pump that inserts partway into the hydrophobic domain. Thus these pumps act as liner mechanochemical devices, and conformations analyzed by different means are represented by different locations of mobile pump sector.

References
 1. Andersen, J. P., B. Vilsen, J. H. Collins, and P. L. Jøkgensen. Localization of E1‐E2 conformational transitions of sarcoplasmic reticulum Ca2+‐ATPase by tryptic cleavage and hydrophobic labeling. J. Membr. Biol. 93: 85–92,1986.
 2. Anderson, R. E., D. M. Woodbury, and W. S. Jee. Humoral and ionic regulation of osteoclast acidity. Calcif. Tissue Int. 39: 252–258, 1986.
 3. Bandopadhyay, S., P. K. Das, M. V. Wright, J. Nandi, D. Bhattacharyyay, and T. K. Ray. Characteristics of a pure endogenous activator of the gastric H+,K+‐ATPase system. J. Biol. Chem. 262: 5664–5670, 1987.
 4. Berglindh, T., D. R. Dibona, C. S. Pace, and G. Sachs. ATP dependence of H+ secretion. J. Cell Biol. 85: 392–401, 1980.
 5. Berglindh, T. O., H. F. Helander, and K. J. Obrink. Effects of secretagogues on oxygen consumption, aminopyrine accumulation and morphology on isolated gastric glands. Acta Physiol. Scand. 97: 401–414, 1976.
 6. Blasie, J. K., L. Herbette, and J. Pachence. Biological membrane structure as seen by X‐ray and neutron diffraction techniques. J. Membr. Biol. 86: 1–8, 1985.
 7. Cantley, L. C., L. G. Cantley, and L. Josephson. A characterization of vanadate interactions with the (Na,K)‐ATPase. J. Biol. Chem. 253: 7361–7368, 1978.
 8. Chang, H., G. Saccomani, E. Rabon, R. Schackmann, and G. Sachs. Proton transport by gastric membrane vesicles. Biochim. Biophys. Acta 464: 313–327, 1977.
 9. Cuppoletti, J., and G. Sachs. Regulation of gastric acid secretion via modulation of a chloride conductance. J. Biol. Chem. 259: 14952–14959, 1984.
 10. Deisenhofer, J., O. Epp, K. Miki, R. Huber, and H. Michel. Structure of the protein subunits in the photoreaction center in the photosynthetic reaction center of Rhodopseudomonas viridis at three angstrom resolution. Nature Load. 318: 618–624, 1985.
 11. DeJong, M. Conformational Changes of H+,K+‐ATPase. Nijmegen, Netherlands: University of Nijmegen, 1986. Dissertation.
 12. Demarest, J. R., and T. E. Machen. Microelectrode measurements form oxyntic cells in intact Necturus gastric mucosa. Am. J. Physiol. 249 (Cell Physiol. 18): C535–C540, 1985.
 13. Durbin, R. P. Electrical potential difference of the gastric mucosa. In: Handbook of Physiology. Alimentary Canal. Secretion, edited by C. F. Code. Washington, DC: Am. Physiol. Soc., 1967, sect. 6, vol. II, chapt. 49, p. 879–888.
 14. Durbin, R. P., F. Michelangeli, and A. Nickel. Active transport and ATP in frog gastric mucosa. Biochim. Biophys. Acta 3367: 177–189, 1974.
 15. Dux, L., P. Slawomir, N. Mullner, and A. Martonosi. Crystallization of Ca2+‐ATPase in detergent‐solubilized sarcoplasmic reticulum. J. Biol. Chem. 262: 6439–6443, 1987.
 16. Elander, B., E. Fellenius, R. Leth, L. Olbe, and B. Wallmark. Inhibitory action of omeprazole on acid formation in gastric glands and on H+,K+‐ATPase isolated from human gastric mucosa. Scand. J. Gastroenterol. 12: 268–272, 1986.
 17. Epstein, M., Y. Kuriki, R. Biltonen, and E. Racker. Calorimetric studies of ligand‐induced modulation of calcium adenosine 5'‐triphosphatase from sarcoplasmic reticulum. Biochemistry 19: 5565–55138, 1980.
 18. Fain, G., A. Smolka, M. C. Cilluffo, M. J. Fain, D. A. Lee, N. C. Brecha, and G. Sachs. Monoclonal antibodies to the H+,K+‐ATPase of gastric mucosa selectively stained the non‐pigmented cell of the rabbit ciliary body epithelium. Invest. Ophthamol. Visual Sci. 29: 785–794, 1988.
 19. Faller, L. D., and G. A. El Gavish. Catalysis of 18O exchange between inorganic phosphate and water by gastric H+,K+‐ATPase. Biochemistry 23: 6584–6590, 1984.
 20. Faller, L., R. Jackson, D. Malinowska, E. Mukidjam, E. Rabon, G. Saccomani, G. Sachs, and A. Smolka. Mechanistic aspects of gastric (H+ + K+)‐ATPase. Ann. NY Acad. Sci. 402: 146–163, 1982.
 21. Faller, L. D., E. Rabon, and G. Sachs. Vanadate binding to the gastric H+,K+‐ATPase. Biochemistry 22: 4676–4685, 1983.
 22. Farley, R. A., and L. D. Faller. Amino acid sequence of an active site peptide from H+,K+‐ATPase of gastric mucosa. J. Biol. Chem. 260: 3899–3901, 1985.
 23. Fellenius, E., T. Berglindh, G. Sachs, L. Olbe, B. Elander, S. E. Sjöstrand, and B. Wallmark. Substituted benzimidazoles block acid secretion by blocking the H+,K+‐ATPase. Nature Lond. 290: 159–161, 1981.
 24. Forte, J. G., J. A. Black, T. M. Forte, T. E. Machen, and J. M. Wolosin. Ultrastructural changes related to functional activity in gastric oxyntic cells. Am. J. Physiol. 241 (Gastrointest. Liver Physiol. 4): G349–358, 1981.
 25. Forte, J. G., A. L. Ganser, and A. S. Tanisawa. The K+ stimulated ATPase system of microsomal oxyntic cells. Ann. NY Acad. Sci. 242: 255–267, 1974.
 26. Forte, J. G., J. L. Poulter, R. Dykstra, J. Rivas, and H. C. Lee. Specific modification of gastric K+‐stimulated ATPase activity by thimerosal. Biochim. Biophys. Acta 644: 257–265, 1981.
 27. Ganser, A. L., and J. G. Forte. K+‐ATPase activity in purified microsomes of bullfrog oxyntic cells. Biochim. Biophys. Acta 307: 169–180, 1973.
 28. Garg, L., and N. Narang. Ouabain‐insensitive K+‐ATPase activity in distal nephron segments (Abstract). Federation Proc. 46: 363, 1987.
 29. Garty, H., B. Rudy, and S. J. D. Karlish. A simple and sensitive procedure for measuring isotope flux through ion specific channels in heterogeneous populations of membrane vesicles. J. Biol. Chem. 258: 169–175, 1983.
 30. Glynn, I. M., and S. J. D. Karlish. The sodium pump. Anna. Rev. Physiol. 37: 13–55, 1975.
 31. Gunther, R. D., S. Bassilian, and E. C. Rabon. Conductance properties of stimulated rabbit vesicles. J. Biol. Chem. 262: 13966–13972, 1987.
 32. Gustin, M. C., and D. P. Goodman. Isolation of brush border membrane from rabbit descending colon epithelium. J. Biol. Chem. 265: 10651–10656, 1981.
 33. Gustin, M. C., and D. B. Goodman. Characterization of the phosphorylated intermediate of K+‐ATPase of rabbit colon brush border membrane. J. Biol. Chem. 257: 9629–9633, 1982.
 34. Hager, K., and C. W. Slayman. Amino acid sequence of the plasma membrane ATPase of Neurospora crassa: deduction from genomic and cDNA sequence. Proc. Natl. Acad. Sci. USA 83: 7693–7697, 1986.
 35. Hangel, D. K., T. Urushidaki, and J. G. Forte. Phosphorylation of microtubule‐associated proteins in gastric glands (Abstract). Federation Proc. 46: 1082, 1987.
 36. HARA, Y., and M. Nakao. ATP‐dependent proton uptake by proteoliposomes reconstituted with purified Na+,K+‐ATPase. J. Biol. Chem. 261: 12655–12658, 1986.
 37. Harris, J. B., and I. S. Edelman. Transport of potassium by the gastric mucosa of the frog. Am. J. Physiol. 198: 280–284, 1960.
 38. Harris, J. B., H. Frank, and I. S. Edelman. Effect of potassium on ion transport and bioelectric potentials of frog gastric mucosa. Am. J. Physiol. 195: 499–504, 1958.
 39. Helander, H. F., and B. I. Hirschowitz. Quantitative ultrastructural studies on gastric parietal cell. Gastroenterology 63: 951–961, 1972.
 40. Helander, H. F., C. H. Ramsay, and C. G. Regardh. Localization of omeprazole and metabolites in the mouse. Scand. J. Gastroenterol. 108: 95–104, 1985.
 41. Helander, H. F., and G. Sachs. Effects of secretagogues on parietal cell morphology in rat. IUPS Symposium, Univ. of Calgary, in press.
 42. Helmich‐DeJong, M. L., J. P. Van Duynhoven, F. M. Schuurmans‐Stekhoven, and J. J. De Pont. Eosin, a fluorescent marker for the high affinity ATPase of H+,K+‐ATPase. Biochim. Biophys. Acta 858: 254–262, 1986.
 43. Helmich‐DeJong, M. L., S. E. Van Emst de Vries, J. J. De Pont, F. M. Schuurmans‐Stekhoven, and S. L. Bonting. Direct evidence for an ADP‐sensitive phosphointermediate of the H+,K+‐ATPase. Biochim. Biophys. Acta 821: 377–383, 1985.
 44. Hersey, S. J., and L. Steiner. Stimulation of acid formation in permeable gastric glands by valinomycin. Am. J. Physiol. 255 (Gastrointest. Liver Physiol. 18): G313–G318, 1988.
 45. Hesse, J. E., L. Wieczorek, K. H. Altendorf, A. S. Reicin, E. Dorus, and W. Epstein. Sequence homology between two membrane transport ATPases, the Kdp‐ATPase of Escherichia coli and the Ca2+‐ATPase of sarcoplasmic reticulum. Proc. Natl. Acad. Sci. USA 81: 4746–4750, 1984.
 46. Hille, B. Ionic Channels of Excitable Membranes. Boston, MA: Sinauer, 1984, p. 226–249.
 47. Hirst, B. A., and J. G. Forte. Redistribution and characterization of H+,K+‐ATPase membranes from resting and stimulated gastric parietal cells. Biochem. J. 231: 641–649, 1985.
 48. Hogben, C. A. M. Biological aspects of active chloride transport. In: Electrolytes in Biological Systems, edited by A. M. Shanes. Washington, DC: Am. Physiol. Soc., 1955, p. 176–204.
 49. Im, W. B., and D. P. Blakeman. Protective effect of EGTA on rat gastric membranes enriched in gastric H+,K+‐ATPase. Biochem. Biophys. Res. Commun. 180: 635–639, 1982.
 50. Im, W. B., D. P. Blakeman, and J. P. Davis. Studies on K+ permeability of rat gastric microsomes. J. Biol. Chem. 260: 9452–9460, 1985.
 51. Im, W. B., D. P. Blakeman, and J. P. Davis. Finding of a KCl‐independent, electrogenic and ATP‐driven H+ pumping activity in rat light gastric microsomes and its effect on the membrane K+ transport activity. J. Biol. Chem. 261: 11686–11692, 1986.
 52. Im, W. B., D. P. Blakeman, J. M. Fieldhouse, and E. C. Rabon. Effect of carbachol or histamine stimulation on rat gastric membranes enriched in H+,K+‐ATPase. Biochim. Biophys. Acta 772: 167–175, 1984.
 53. Im, W. B., D. P. Blakeman, J. Mendlein, and G. Sachs. Inhibition of (H+ + K+)‐ATPase and H+ accumulation in hog gastric membranes by trifluoperazine, verapamil and 8‐(N,N‐diethylamino)octyl‐3,4,5‐trimethoxybenzoate. Biochim. Biophys. Acta 770: 65–72, 1984.
 54. Im, W. B., D. P. Blakeman, and G. Sachs. Reversal of antisecretory activity of omeprazole by sulfhydryl compounds in isolated rabbit gastric glands. Biochim. Biophys. Acta 845: 54–59, 1985.
 55. Im, W. B., J. P. Davis, and D. P. Blakeman. Preparation of rat gastric heavy and light microsomal membranes enriched in (H+ + K+)‐ATPase using 2H20 and Percoll gradients. Biochem. Biophys. Res. Commun. 131: 905–911, 1985.
 56. Jackson, R. J., J. Mendlein, and G. Sachs. Interaction of fluorescein isothiocyanate with the H+,K+‐ATPase. Biochim. Biophys. Acta 731: 9–15, 1983.
 57. Jackson, R. J., and G. Saccomani. Phosphorylation of gastric H+,K+‐ATPase by inorganic phosphate (Abstract). Biophys. J. 45: 83, 1984.
 58. Kaplan, J. D. Ion movements through the sodium pump. Annu. Rev. Physiol. 47: 535–544, 1985.
 59. Karlish, S. J. D., W. R. Lieb, and W. D. Stein. Combined effects of ATP and phosphate on Rb+ exchange mediated by Na+,K+‐ATPase reconstituted into phospholipid vesicles. J. Physiol. Lond. 328: 333–350, 1982.
 60. Karlish, S. J. D., and U. Pick. Sidedness of the effects of sodium and potassium on the conformational state of the sodium potassium pump. J. Physiol. Lond. 312: 505–529, 1981.
 61. Kasbekar, D. K. Potassium selectivity of frog gastric luminal membrane. Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G765–G772, 1986.
 62. Kaunitz, J., and G. Sachs. Identification of a vanadate‐sensitive, potassium‐dependent proton pump from rabbit colon. J. Biol. Chem. 261: 14005–14010, 1986.
 63. Keeling, D. J., C. Fallowfield, and A. H. Underwood. The specificity of omeprazole as an H+,K+‐ATPase inhibitor depends upon the means of its activation. Biochem. Pharmacol. 36: 339–344, 1987.
 64. Koelz, H. R., G. Sachs, and T. Berglindh. Cation effects on acid secretion in rabbit gastric glands. Am. J. Physiol. 241 (Gastrointest. Liver Physiol. 4): G431–G442, 1981.
 65. Koenig, C. S. Redistribution of gastric K+ pNNPase in vertebrate oxyntic cells in relation to hydrochloric acid secretion: a cytochemical study. Anat. Rec. 210: 583–596, 1984.
 66. Kyte, J., and R. F. Doolittle. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157: 105–132, 1983.
 67. Lane, L. K., T. K. Kirley, and W. J. Ball. Structural studies on H+,K+‐ATPase: determination of the NH2 terminal amino acid sequence and immunological cross reactivity with Na+,K+‐ATPase. Biochem. Biophys. Res. Commun. 138: 185–192, 1986.
 68. Larsson, H., E. Carlsson, B. Ryberg, J. Fryklund, and B. Wallmark. Rat parietal cell function after prolonged inhibition of gastric acid secretion. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G33–G39, 1988.
 69. Lee, H. C., and J. G. Forte. A study of H+ transport in gastric microsomal vesicles using fluorescent probes. Biochim. Biophys. Acta 508: 339–356, 1978.
 70. Lee, H. C., and J. G. Forte. Chemical modification of gastric microsomal potassium‐stimulated ATPase. Biochim. Biophys. Acta 598: 595–605, 1980.
 71. Lee, J., G. Simpson, and P. Scholes. An ATPase from dog gastric mucosa: changes of outer pH in suspensions of membrane vesicles accompanying ATP hydrolysis. Biochem. Biophys. Res. Commun. 60: 825–832, 1974.
 72. Lewin, M. J. M., G. Saccomani, R. Schackmann, and G. Sachs. The use of ANS as a probe of gastric vesicle transport. J. Membr. Biol. 32: 301–318, 1977.
 73. Lind, T., C. Cederberg, G. Ekenved, U. Haglund, and L. Olbe. Effect of omeprazole, a gastric proton pump inhibitor, on pentagastrin‐stimulated acid secretion in man. Gut 24: 270–276, 1983.
 74. Ljungström, M., and S. Mårdh. Kinetics of the acid pump in the stomach. Proton transport and hydrolysis of ATP and p‐nitrophenyl phosphate by the gastric H+,K+‐ATPase. J. Biol. Chem. 260: 5440–5444, 1985.
 75. Ljungström, M., L. Norberg, H. Olaisson, C. Wernstedt, F. V. Vega, G. Arvidson, and S. Mårdh. Characterization of proton‐transporting membranes from resting pig gastric mucosa. Biochim. Biophys. Acta 769: 209–219, 1984.
 76. LjungstrOm, M., F. V. Vega, and S. Mårdh. Effects of pH on the interaction of ligands with the (H+ + K+)‐ATPase purified from pig gastric mucosa. Biochim. Biophys. Acta 769: 220–230, 1984.
 77. Long, J. F., P. J. S. Chiu, M. J. Derelanko, and M. Steinberg. Gastric antisecretory and cytoprotective activities of SCH 28080. J. Pharmacol. Exp. Ther. 226: 114–120, 1983.
 78. Lorentzon, P., B. Eklundh, A. Brändström, and B. Wallmark. The mechanism for inhibition of gastric H+,K+‐ATPase by omeprazole. Biochim. Biophys. Acta 778: 549–558, 1984.
 79. Lorentzon, P., R. Jackson, B. Wallmark, and G. Sachs. Inhibition of H+,K+‐ATPase by omeprazole in isolated gastric vesicles requires proton transport. Biochim. Biophys. Acta 897: 41–51, 1987.
 80. Malinowska, D. H., J. Cuppoletti, and G. Sachs. CI‐ requirement of acid secretion in isolated gastric glands. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G573–G581, 1983.
 81. Malinowska, D. M., H. R. Koelz, S. J. Hersey, and G. Sachs. Properties of the gastric proton pump in permeable, unstimulated gastric glands. Proc. Natl. Acad. Sci. USA 78: 5908–5912, 1981.
 82. McLennan, D. H., C. J. Brandl, B. Korczak, and N. M. Green. Amino acid sequence of a Ca2+,Mg2+‐dependent ATPase from rabbit muscle sarcoplasmic reticulum, deduced from its complementary DNA sequence. Nature Lond. 316: 696–700, 1985.
 83. Mendlein, J., and G. Sachs. Ca2+ generated form of the H+,K+‐ATPase (Abstract). Federation Proc. 41: 1125, 1982.
 84. Menik, D. R., J. A. Lee, R. J. Brooker, T. H. Wilson, and H. R. Kabak. Role of cysteine residues in Lac permease of E. coli. Biochemistry 26: 1132–1136, 1987.
 85. Moody, F. G. Oxygen consumption during thiocyanate inhibition of gastric acid secretion in dogs. Am. J. Physiol. 215: 127–131, 1968.
 86. Muallem, S., D. Blissard, E. M. Cragoe, and G. Sachs. Role of Na+/H+ exchange in parietal cell function. J. Biol. Chem. In press.
 87. Muallem, S., C. Burnham, T. Berglindh, D. Blissard, and G. Sachs. Electrolyte transport across the basal lateral membrane of the parietal cell. J. Biol. Chem. 260: 6641–6653, 1985.
 88. Muallem, S., and S. J. D. Karlish. Regulation of the Ca2+ pump by calmodulin in the intact cell. Biochim. Biophys. Acta 687: 329–332, 1982.
 89. Munson, K. B., and G. Sachs. Inactivation of H+,K+‐ATPase by a K+ competitive photoaffinity inhibitor. Biochemistry 27: 3932, 1988.
 90. Nandi, J., Z. Men‐Ai, and T. K. Ray. Role of membrane‐associated thiol groups in the functional regulation of gastric microsomal H+,K+‐transporting ATPase system. Biochem. J. 213: 587–594, 1983.
 91. Nandi, J., M. V. Wright, and T. K. Ray. Mechanism of gastric antisecretory effects of nolinium bromide. Gastroenterology 85: 938–945, 1983.
 92. Ottolenghi, P., J. G. Morby, and J. Jensen. Solubilization and further chromatographic purification of highly purified, membrane‐bound Na+,K+‐ATPase. Biochem. Biophys. Res. Commun. 135: 1008–1014, 1986.
 93. Ovchinnikov, Y. A., N. N. Modyanov, N. E. Broude, K. E. Petruhkin, A. V. Grishin, N. M. Arzamazova, N. A. Aldanova, G. S. Monastyrskaya, and E. S. Sverdlov. Pig kidney Na+,K+‐ATPase. FEBS Lett. 201: 237–245, 1986.
 94. Paradiso, A. M., R. Y. Tsien, and T. E. Machen. Na+/H+ exchange in gastric glands as measured with a cytoplasmic trapped fluorescent pH indicator. Proc. Natl. Acad. Sci. USA 81: 7436–7440, 1984.
 95. Peters, W. H., A. M. Fleuren‐Jakobs, J. J. Schrijen, J. J. De Pont, and S. L. Bonting. Studies on (H+ + K+)‐ATPase. V. Chemical composition and molecular weight of the catalytic subunit. Biochim. Biophys. Acta 688: 803–807, 1982.
 96. Pick, U., and S. Bassilian. The effects of ADP, phosphate and arsenate on Ca2+ efflux from sarcoplasmic reticulum vesicles. Eur. J. Biochem. 131: 393–399, 1983.
 97. Plesner, I. W., L. Plesner, J. G. Norby, and I. Klodos. The steady state kinetic mechanism of ATP hydrolysis catalyzed by membrane bound Na+,K+‐ATPase from ox brain. Biochim. Biophys. Acta 643: 483–494, 1981.
 98. Post, R. L., C. Hegyvary, and S. Kume. Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J. Biol. Chem. 247: 6530–6540, 1972.
 99. Post, R. L., G. Toda, and F. N. Rogers. Phosphorylation by inorganic phosphate of sodium plus potassium ion transport adenosine triphosphatase. J. Biol. Chem. 250: 691–701, 1975.
 100. Rabon, E., H. Chang, and G. Sachs. Quantitation of hydrogen ion and potential gradients in gastric plasma membrane vesicles. Biochemistry 17: 3345–3353, 1978.
 101. Rabon, E., J. Cuppoletti, D. Malinowska, A. Smolka, H. F. Helander, J. Mendlein, and G. Sachs. Proton secretion by the gastric parietal cell. J. Exp. Biol. 106: 119–133, 1983.
 102. Rabon, E., R. D. Gunther, A. Soumarmon, S. Bassilian, M. Lewin, and G. Sachs. Solubilization and reconstitution of the gastric H+,K+‐ATPase. J. Biol. Chem. 260: 10200–10207, 1985.
 103. Rabon, E., T. McFall, and G. Sachs. The gastric H+,K+‐ATPase H+/ATP stoichiometry. J. Biol. Chem. 257: 6296–6299, 1982.
 104. Rabon, E., G. Saccomani, D. K. Kasbekar, and G. Sachs. Transport characteristics of frog gastric membranes. Biochim. Biophys. Acta 551: 432–487, 1979.
 105. Rabon, E., G. Sachs, S. Mardh, and B. Wallmark. ATP/ADP exchange activity of gastric H+,K+‐ATPase. Biochim. Biophys. Acta 688: 515–524, 1982.
 106. Rabon, E., N. Takeguchi, and G. Sachs. Water and salt permeability of gastric vesicles. J. Membr. Biol. 53: 109–117, 1980.
 107. Rabon, E., M. Wilke, G. Sachs, and G. Zampighi. Crystallization of the H+,K+‐ATPase. J. Biol. Chem. 261: 1434–1439, 1986.
 108. Ratnam, M., D. L. Nguyen, J. Rivier, P. B. Sargent, and J. Lindstrom. Transmembrane topography of nicotinic acetylcholine receptor: immunochemical tests contradict theoretical predictions based on hydrophobicity profiles. Biochemistry 25: 2633–2643, 1986.
 109. Ray, T. K., and J. G. Forte. Studies on the phosphorylated intermediates of a K+‐stimulated ATPase from rabbit gastric mucosa. Biochim. Biophys. Acta 443: 451–467, 1976.
 110. Ray, T. K., and J. Nandi. K+‐stimulated p‐nitrophenyl phosphatase is not a partial reaction of the gastric H+,K+‐ATPase. Evidence supporting a new model for the univalent cation‐transporting ATPase systems. Biochem. J. 233: 231–238, 1986.
 111. Reenstra, W. W., and J. G. Forte. H+/ATP stoichiometry for the gastric H+,K+‐ATPase. J. Membr. Biol. 61: 55–60, 1981.
 112. Reggio, H., D. Bainton, E. Harms, E. Coudrier, and D. Louvard. Antibodies against lysosomal membranes reveal a 100,000‐mol‐wt protein that cross‐reacts with purified H+,K+‐ATPase from gastric mucosa. J. Cell Biol. 99: 1511–1526, 1984.
 113. Rehm, W. S. The effect of electric current on gastric secretion and potential. Am. J. Physiol. 144: 115–125, 1945.
 114. Rehm, W. S. Electrophysiology of the gastric mucosa in Cl‐ free solutions. Federation Proc. 24: 1387–1395, 1965.
 115. Rehm, W. S. Proton Transport in Metabolic Transport, edited by L. E. Hokin. New York: Academic, 1972, p. 188–241.
 116. Saccomani, G., M. L. Barcellona, and G. Sachs. Site‐directed modifications of gastric H+,K+‐ATPase in hydrogen ion transport. In: Epithelia, edited by I. Schulz, G. Sachs, J. Forte, and K. J. Ullrich. New York: Elsevier, 1980, p. 175–184.
 117. Saccomani, G., M. L. Barcellona, and G. Sachs. Reactivity of gastric (H+ + K+)‐ATPase to N‐ethoxycarbonyl‐2‐ethoxy‐1,2–dihydroquinoline. J. Biol. Chem. 256: 12405–12410, 1981.
 118. Saccomani, G., H. H. Chang, A. A. Mihas, S. Crago, and G. Sachs. An acid transporting enzyme in human gastric mucosa. J. Clin. Invest. 64: 627–635, 1979.
 119. Saccomani, G., H. H. Chang, A. Spisni, H. F. Helander, H. L. Spitzer, and G. Sachs. Effect of phospholipase A2 on purified gastric vesicles. J. Supramol. Struct. 11: 429–444, 1979.
 120. Saccomani, G., L. Cole, and E. Mukidjam. Interaction of photoaffinity label 8‐azido ATP with the gastric H+,K+‐ATPase. In: Hydrogen Ion Transport in Epithelia, edited by J. G. Forte, D. G. Warnock, and R. C. Rector. New York: Wiley‐Interscience, 1984, p. 195–208.
 121. Saccomani, G., D. W. Dailey, and G. Sachs. The action of trypsin on the gastric (H+ + K+)‐ATPase. J. Biol. Chem. 254: 2821–2827, 1979.
 122. Saccomani, G., H. F. Helander, S. Crago, H. H. Chang, D. W. Dailey, and G. Sachs. Characterization of gastric mucosal membranes. X. Immunological studies of gastric (H+ + K+)‐ATPase. J. Cell Biol. 83: 271–283, 1979.
 123. Saccomani, G., G. Sachs, J. Cuppoletti, and C. Y. Jung. Target molecular weight of the gastric (H+ + K+)‐ATPase functional and structural molecular size. J. Biol. Chem. 256: 7727–7729, 1981.
 124. Saccomani, G., G. Shah, J. G. Spenney, and G. Sachs. Characterization of gastric mucosal membranes. VIII. Localization of peptides by iodination and phosphorylation. J. Biol. Chem. 250: 4802–4809, 1975.
 125. Saccomani, G., H. B. Stewart, D. Shaw, M. Lewin, and G. Sachs. Characterization of gastric mucosal membranes: fractionation by zonal centrifugation and free flow electrophoresis. Biochim. Biophys. Acta 465: 311–330, 1977.
 126. Sachs, G. H+ transport by a non‐electrogenic ATPase as a model for acid secretion. Rev. Physiol. Biochem. Pharmacol. 79: 133–162, 1977.
 127. Sachs, G. The gastric proton pump: the H+,K+‐ATPase. In: Physiology of the Gastrointestinal Tract, edited by L. R. Johnson. New York: Raven, 1987, vol. 1, p. 865–881.
 128. Sachs, G., T. Berglindh, E. Rabon, H. B. Stewart, M. L. Barcellona, B. Wallmark, and G. Saccomani. Aspects of parietal cell biology: cells and vesicles. Ann. NY Acad. Sci. 341: 312–334, 1980.
 129. Sachs, G., T. Berglindh, E. Rabon, B. Wallmark, M. Barcellona, H. B. Stewart, and G. Saccomani. Interaction of K+ with gastric parietal cells and gastric ATPase. Ann. NY Acad. Sci. 358: 118–137, 1980.
 130. Sachs, G., H. H. Chang, E. Rabon, R. Schackmann, M. Lewin, and G. Saccomani. A nonelectrogenic H+ pump in plasma membranes of hog stomach. J. Biol. Chem. 251: 7690–7698, 1976.
 131. Sachs, G., H. Chang, E. Rabon, R. Schackmann, H. M. Sarau, and G. Saccomani. Metabolic and membrane aspects of gastric H+ transport. Gastroenterology 73: 931–940, 1977.
 132. Sachs, G., J. Cuppoletti, J. Kaunitz, and D. Malinowska. Aspects of H+ translocating ATPases. In: Gastrointestinal and Hepatic Secretions: Mechanisms and Control, edited by J. S. Davison and E. A. Shaffer. Alberta, Canada: Univ. of Calgary Press, 1988.
 133. Sachs, G., R. J. Jackson, and E. C. Rabon. Use of plasma membrane vesicles. Am. J. Physiol. 238 (Gastrointest. Liver Physiol. 1): G151–G164, 1980.
 134. Sarau, H. M., J. Foley, G. Moonsamy, and G. Sachs. Metabolism of dog gastric mucosa. II. Levels of glycolytic, citric acid cycle and other intermediates. J. Biol. Chem. 252: 8572–8581, 1977.
 135. Sarau, H. M., J. Foley, G. Moonsamy, V. D. Wiebelhaus, and G. Sachs. Metabolism of dog gastric mucosa. I. Nucleotide levels in parietal cells. J. Biol. Chem. 280: 83321–83329, 1975.
 136. Schackmann, R., A. Schwartz, G. Saccomani, and G. Sachs. Cation transport by the gastric H+,K+‐ATPase. J. Membr. Biol. 32: 361–381, 1977.
 137. Schrijen, J. J., W. A. Luyben, J. J. De Pont, and S. L. Bonting. Studies on H+,K+‐ATPase. I. Essential arginine residue in its substrate binding center. Biochim. Biophys. Acta 597: 331–344, 1980.
 138. Schrijen, J. J., W. A. Van Groningen‐Luyben, J. J. De Pont, and S. L. Bonting. Studies on (K+ + H+)‐ATPase. II. Role of sulfhydryl groups in its reaction mechanism. Biochim. Biophys. Acta 640: 473–486, 1981.
 139. Schrijen, J. J., W. A. Van Groningen‐Luben, H. Nauta, J. J. De Pont, and S. L. Bonting. Studies on (K+ + H+)ATPase. VI. Determination on the molecular size by radiation inactivation analysis. Biochim. Biophys. Acta 731: 9–15, 1983.
 140. Serrano, R., M. Kielland‐Brandy, and G. R. Fink. Yeast plasma membrane ATPase is essential for growth and has homology with Na+, K+, and Ca2+ ATPase. Nature Lond. 319: 689–693, 1986.
 141. Shull, G. E., and J. B. Lingrel. Molecular cloning of the gastric H+,K+‐ATPase. J. Biol. Chem. 261: 16788–16791, 1986.
 142. Shull, G. E., A. Schwartz, and J. B. Lingrel. Amino acid sequence of the catalytic subunit of the Na+,K+‐ATPase deduced from a complementary DNA. Nature Lond. 316: 691–695, 1985.
 143. Skou, J. C. The Na+,K+ activated enzyme system and its relationship to transport of sodium and potassium. Q. Rev. Biophys. 7: 401–434, 1975.
 144. Skrabanja, A. T., P. Asty, A. Soumarmon, J. Joep, J. J. De Pont, and M. J. Lewin. H+ transport by reconstituted gastric H+,K+‐ATPase. Biochim. Biophys. Acta 860: 131–136, 1986.
 145. Skrabanja, A. T., J. J. De Pont, and S. L. Bonting. H+/ATP transport ratio of the H+,K+‐ATPase of pig gastric membrane vesicles. Biochim. Biophys. Acta 774: 91–95, 1984.
 146. Smith, G. S., and P. B. Scholes. The H+/ATP stoichiometry of the H+,K+‐ATPase of dog gastric microsomes. Biochim. Biophys. Acta 688: 803–807, 1982.
 147. Smolka, A. K., H. F. Helander, and G. Sachs. Monoclonal antibodies against the gastric H+,K+‐ATPase. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G589–G596, 1983.
 148. Smolka, A., and P. Lorentzon. In vitro synthesis of gastric proteins. In: IUPS Symposium, Calgary. Alberta, Canada: Univ. of Calgary Press, 1988.
 149. Soumarmon, A., M. Abastado, S. Bonfils, and M. J. Lewin. Chloride transport in gastric microsomes: an ATP‐dependent influx sensitive to membrane potential and to protein kinase inhibitor. J. Biol. Chem. 255: 11662–11687, 1980.
 150. Soumarmon, A., and M. J. Lewin. Gastric H+,K+‐ATPase. Biochimie Paris 68: 1287–1291, 1986.
 151. Soumarmon, A., P. Rangachari, and M. Lewin. Passive transport of Rb+ by hog gastric H+,K+‐ATPase. J. Biol. Chem. 259: 11861–11867, 1984.
 152. Stewart, H. B., B. Wallmark, and G. Sachs. The interaction of H+ and K+ with the partial reactions of gastric H+,K+‐ATPase. J. Biol. Chem. 256: 2682–2690, 1981.
 153. Sugai, N. A., and S. Ito. Carbonic anhydrase, ultrastructural localization in marine gastric mucosa and improvements in technique. J. Histochem. Cytochem. 28: 511–525, 1980.
 154. Sussman, M. R., and C. W. Slayman. Modification of Neurospora crassa plasma membrane proton translocating ATPase with N,N‐dicyclocarbodiimide. J. Biol. Chem. 258: 1839–1843, 1983.
 155. Tougard, C., D. Louvard, R. Picart, and A. Tixier‐Vidal. Antibodies against a lysosomal membrane antigen recognize a prelysosomal compartment involved in the endocytic pathway in cultured prolactin cells. J. Cell Biol. 100: 786–793, 1985.
 156. Tuukkanen, J., and H. K. Väänänen. Omeprazole, a specific inhibitor of H*‐K+‐ATPase, inhibits bone resorption in vivo. Calcif. Tissue Int. 38: 123–125, 1986.
 157. Ueda, S., D. Loo, and G. Sachs. Regulation of K+ channels in basal lateral membrane of Necturus oxyntic cells. J. Membr. Biol. 97: 31–41, 1987.
 158. Vasallo, P. M., and R. L. Post. Calcium ion as a probe of the monovalent cation center of sodium potassium ATPase. J. Biol. Chem. 261: 16957–16962, 1986.
 159. Vega, F. V., H. Olaisson, and S. Mårdh. Distribution of carbonic anhydrase in cells and membranes isolated from pig gastric mucosa. Acta Physiol. Scand. 124: 573–579, 1985.
 160. Walan, A. Clinical perspectives of drugs inhibiting acid secretion—H+‐K+‐ATPase inhibitors. Scand. J. Gastroenterol. 125: 50–54, 1986.
 161. Walderhaug, M. O., R. L. Post, G. Saccomani, R. T. Leonard, and D. P. Briskin. Structural relatedness of three ion‐transport adenosine triphosphatases around their active sites of phosphorylation. J. Biol. Chem. 260: 3852–3859, 1985.
 162. Wallace, B. A. Evaluation of methods for prediction of membrane protein secondary structure. Proc. Natl. Acad. Sci. USA 83: 9423–9428, 1986.
 163. Wallmark, B. Mechanism of action of omeprazole. Scand. J. Gastroenterol. 118: 11–17, 1986.
 164. Wallmark, B., A. Brändström, and H. Larsson. Evidence for acid‐induced transformation of omeprazole into an active inhibitor of H+,K+‐ATPase within the parietal cell. Biochim. Biophys. Acta 778: 549–558, 1984.
 165. Wallmark, B., C. Briving, J. Fryklund, K. Munson, R. Jackson, J. Mendlein, E. Rabon, and G. Sachs. Inhibition of gastric H+,K+‐ATPase and acid secretion by SCH 28080, a substituted pyridyl ,2α)‐imidazole. J. Biol. Chem. 262: 2077–2084, 1987.
 166. Wallmark, B., E. Carlsson, H. Larsson, A. Brändström, and P. Lindberg. New inhibitors of gastric acid secretion: properties and design of H+,K+‐ATPase blockers. In: SCI‐RSC Medicinal Chemistry Symposium 3rd, London, edited by R. W. Lambert. 1985, p. 293–311.
 167. Wallmark, B., H. Larsson, and L. Humble. The relationship between gastric acid secretion and gastric H+,K+‐ATPase. J. Biol. Chem. 260: 13681–13684, 1985.
 168. Wallmark, B., and S. Mårdh. Phosphorylation and dephosphorylation kinetics of potassium‐stimulated ATP phospho‐hydrolase from hog gastric mucosa. J. Biol. Chem. 254: 11899–11902, 1979.
 169. Wallmark, B., G. Sachs, S. Mårdh, and E. Fellenius. Inhibition of gastric H+,K+‐ATPase by substituted benzimidazole, picoprazole. Biochim. Biophys. Acta 728: 31–38, 1983.
 170. Wallmark, B., H. B. Stewart, E. Rabon, G. Saccomani, and G. Sachs. The catalytic cycle of the gastric H+‐,K+‐ATPase. J. Biol. Chem. 255: 5313–5319, 1980.
 171. Wolosin, J. M. Ion transport studies with H+K+‐ATPase‐rich vesicles: implications for HCl secretion and parietal cell physiology. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G595–G607, 1985.
 172. Wolosin, J. M., and J. G. Forte. Changes in the membrane environment of the H+,K+‐ATPase following stimulation of the gastric oxyntic cell. J. Biol. Chem. 256: 3149–3152, 1981.
 173. Wolosin, J. M., and J. G. Forte. Kinetic properties of the KCl transport at the secreting apical membrane of the oxyntic cell. J. Membr. Biol. 71: 195–207, 1983.
 174. Wolosin, J. M., and J. G. Forte. K+ and CI‐ conductances in the apical membranes from secreting oxyntic cells are concurrently inhibited by divalent cations. J. Membr. Biol. 83: 261–272, 1985.
 175. Zibirve, R., G. H. Feldman, J. Kuhne, P. Porznik, G. Warnecke, and G. Koch. Detection and localization of a cytoplasmic domain on the subunit of the Na+,K+‐ATPase: a monoclonal antibody study. J. Biol. Chem. 262: 4349–4354, 1987.

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Article Title: Biochemistry of Gastric Acid Secretion: H+‐K+‐ATPase
 

How to Cite

G. Sachs, J. Kaunitz, J. Mendlein, B. Wallmark. Biochemistry of Gastric Acid Secretion: H+‐K+‐ATPase. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 229-253. First published in print 1989. doi: 10.1002/cphy.cp060312