Mechanisms of H+ injury in rabbit esophageal epithelium

Abstract

We previously postulated that active Na transport by the esophageal stratified squamous epithelium is important for maintenance of its barrier function. To investigate this further we studied the effects of HCl on the in vivo esophageal potential difference (PD), on in vitro Na transport, and on esophageal Na-K-ATPase activity. In vivo esophageal perfusion with low concentrations of HCl (20 or 40 mM) increased the PD and a high concentration (120 mM) decreased it. An intermediate concentration (80 mM) caused a biphasic response with an initial increase in PD followed by a progressive decrease in PD. In vitro transport studies were performed to explain the increased in vivo PD. In the presence of luminal H+ the increased PD resulted from H+ diffusion from lumen to blood, whereas after H+ exposure the increased PD was due largely to increased net Na transport from lumen to blood through an amiloride-sensitive mechanism. In tissues with prolonged exposure to 80 mM HCl (PD decreased 80-100%), Na-K-ATPase activity was significantly inhibited (1.94 +/- 0.32 vs. 5.12 +/- 0.73 mumol P X mg prot-1 X h-1). Thus, HCl initially increases the in vivo esophageal PD by H+ transport from lumen to blood, a process replaced by stimulated net Na transport when H+ is replaced by Na. Prolonged acid exposure ultimately decreases Na exit from cells by inhibiting Na-K-ATPase activity. This sequence suggests that alterations in Na transport could result in cell edema and necrosis via loss of cell volume regulation.

Sex and Gender Differences in Gastroesophageal Reflux Disease

“…13,60,63 Chronic exposure to gastric acid and other intra-esophageal materials such as bile and alcohol can disrupt the esophageal barrier function. 63,64 Reduced levels of E2 due to aging, especially, after women's menopause, can potentially increase epithelial permeability and microbial translocation (Fig. 3).…”

“…Such a mechanism of estrogen might explain the male predominance of GERD. [63][64][65] Honda et al 63 conducted an animal study to identify the role of estrogen treatment on the esophageal epithelial barrier function and found that 17β-estradiol administration reduced the dilation of the intercellular space caused by luminal irritants. Moreover, 17β-estradiol administration increased the expression of occludin.…”

THE EFFECT OF DIET, INTRARUMINAL pH AND OSMOLARITY ON SODIUM, CHLORIDE AND MAGNESIUM ABSORPTION FROM THE TEMPORARILY ISOLATED AND WASHED RETICULO‐RUMEN OF SHEEP

“…Both (Orlando, Bryson & Powell, 1984), frog skin (Fischbarg & Whittembury, 1978;Ferreira & Hill, 1982), toad bladder (Wade, Revel & Di Scala, 1973) and rumen (Gemmel & Stacy, 1973;Gaebel, Suendermann & Martens, 1987). In ruminants, a drop in pH and a rise in rumen fluid osmolarity are the consequences of a sudden high intake of easily fermentable carbohydrates and the resulting rumen acidosis (Kezar & Church, 1979).…”

Chloride transport in rabbit esophageal epithelial cells

“…(Table 2). 16.4 Ϯ 2.1 to 9.9 Ϯ 1.5 mM (n ϭ 13, P Ͻ 0.001). This was accompanied by a very rapid (Ͻ1 min) initial depolarization of V mBL (Fig.…”

“…Although the contribution of Cl Ϫ to the short-circuit current is very small, cellular transport of Cl Ϫ , similar to other epithelia, is fundamental for the maintenance of the intracellular milieu. Regulation of cellular Cl Ϫ transport is particularly important in the esophageal epithelium, a tissue regularly exposed to wide fluctuations in luminal content including high levels of NaCl (salt) in food and HCl (gastric acid) due to the reflux of gastric content (14,16). Because very little information is available about Cl Ϫ transport in esophageal epithelial cells, the purpose of this study was to examine its transport pathways across both the basolateral and the apical cell membranes of this epithelium.…”