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. MATERIAL AND 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.

journal_name

Scand J Gastroenterol

authors

Herrmann M,Selige J,Raffael S,Sachs G,Brambilla A,Klein T

doi

10.1080/00365520701405579

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

1275-88

issue

11

eissn

0036-5521

issn

1502-7708

pii

780566734

journal_volume

42

pub_type

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