title: Systematic expression profiling of the gastric H+/K+ ATPase in human tissue.
abstract: OBJECTIVE
  The potassium-competitive acid blockers (P-CABs), comprise a new, innovative group of competitive and reversible inhibitors of the gastric H+/K+ ATPase. Our aim was to identify sites of expression of the H+/K+ ATPase that are potential targets of these compounds by examining the expression profile of the gastric H+/K+ ATPase in the human body from a broad range of tissues.
  
  
  METHODS
  Expression profiling was done by quantitative mRNA analysis (TaqMan PCR). Tissues that were mRNA-positive for the alpha subunit were investigated further by Western blot and immunohistochemistry (IHC) for the presence of gastric H+/K+ ATPase protein.
  
  
  RESULTS
  In addition to the very high expression levels in the stomach, the adrenal gland, cerebellum and pancreas gave unexpectedly positive mRNA signals for the alpha subunit of gastric H +/K+ ATPase. However, they were negative for mRNA of the beta subunit, and Western blot and IHC were negative for alpha and beta subunit protein. Another group of tissues with low alpha subunit mRNA expression including the frontal cortex, cortex grey matter, testis, thymus and larynx submucosa were also found negative for both alpha and beta subunit protein. In contrast to mouse kidney, no gastric H+/K+ ATPase could be detected in human kidney.
  
  
  CONCLUSIONS
  We therefore conclude that the only organ in humans expressing significant levels of the P-CAB target gastric H+/K+ ATPase is the stomach.
authors.affiliation: Department of Biochemistry Gastroenterology, ALTANA Pharma AG, Konstanz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Herrmann
authors.forename: Jens
authors.initials: J
authors.lastname: Selige
authors.forename: Sandra
authors.initials: S
authors.lastname: Raffael
authors.forename: George
authors.initials: G
authors.lastname: Sachs
authors.forename: Andrea
authors.initials: A
authors.lastname: Brambilla
authors.forename: Thomas
authors.initials: T
authors.lastname: Klein
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology; D015153:Blotting, Western; D002531:Cerebellum / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D005260:Female; D020869:Gene Expression Profiling; D017506:H(+)-K(+)-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology; D007830:Larynx / Q000201:enzymology; D008297:Male; D010179:Pancreas / Q000201:enzymology; D016133:Polymerase Chain Reaction / Q000379:methods; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013270:Stomach / Q000201:enzymology; D013737:Testis / Q000201:enzymology; D013950:Thymus Gland / Q000201:enzymology
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D017506:H(+)-K(+)-Exchanging ATPase