Review article: the control of gastric acid and Helicobacter pylori eradication.
This review focuses on the gastric acid pump as a therapeutic target for the control of acid secretion in peptic ulcer and gastro-oesophageal reflux disease. The mechanism of the proton pump inhibitors is discussed as well as their clinical use. The biology of Helicobacter pylori as a gastric denizen is then discussed, with special regard to its mechanisms of acid resistance. Here the properties of the products of the urease gene clusters, ureA, B and ureI, E, F, G and H are explored in order to explain the unique location of this pathogen. The dominant requirement for acid resistance is the presence of a proton gated urea transporter, UreI, which increases access of gastric juice urea to the intrabacterial urease 300-fold. This enables rapid and continuous buffering of the bacterial periplasm to approximately pH 6.0, allowing acid resistance and growth at acidic pH in the presence of 1 mM urea. A hypothesis for the basis of combination therapy for eradication is also presented.
Sachs
G
G
UCLA Digestive Research Center, Departments of Physiology and Medicine, University of California, Los Angeles, CA, USA. gsachs@ucla.edu
Shin
J M
JM
Munson
K
K
Vagin
O
O
Lambrecht
N
N
Scott
D R
DR
Weeks
D L
DL
Melchers
K
K
D005744:Gastric Acid / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase / Q000187:drug effects / Q000502:physiology; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000382:microbiology; D054328:Proton Pump Inhibitors; D014510:Urease / Q000235:genetics* / Q000502:physiology
D054328:Proton Pump Inhibitors; D014510:Urease; D017506:H(+)-K(+)-Exchanging ATPase