Regulation of Na/H exchanger-1 in gastroesophageal reflux disease: possible interaction of histamine receptor.
Na/H exchanger-1 (NHE-1) isoform regulates intracellular pH and protects the esophageal mucosa. These functions are compromised in gastroesophageal reflux disease (GERD); however, the role and the underlying mechanism of NHE-1 regulation are obscure. To address this issue, NHE-1 protein and mRNA levels were measured by ECL western blot analysis and a semiquantitative RT-PCR using alpha-actin as an internal control. Ouabain-sensitive and K-stimulated p-nitrophenylphosphatase activity was measured as a marker of the sodium pump. The level of NHE-1 protein and mRNA and sodium pump activity was increased in GERD patients with or without esophagitis. Interestingly, myeloperoxidase (MPO) activity and infiltration of inflammatory cells were significantly increased in the GERD patients with esophagitis as compared to the GERD without esophagitis and the normal controls. This induction of NHE-1 and sodium pump was reversed in the GERD patients taking an H2 blocker, but not in those taking antacids. The internal control alpha-actin did not change under these conditions. Yield of total RNA and crude microsomal proteins was also statistically similar in all the test groups. These findings demonstrate that induction of NHE-1 is regulated posttranscriptionally through a possible interaction of histamine receptor. Induction of NHE-1 and sodium pump activity together might be a mechanism underlying the GERD pathogenesis and suggests a significance of NHE-1 inhibition in the treatment of GERD.
Siddique
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Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait.
Khan
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D000328:Adult; D015153:Blotting, Western; D005260:Female; D005764:Gastroesophageal Reflux / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000378:metabolism; D011968:Receptors, Histamine / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism* / Q000502:physiology*
D011968:Receptors, Histamine; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D009195:Peroxidase