Differential expression and regulation of Na⁺/H⁺exchanger isoforms in rabbit parietal and mucous cells

Abstract

Several Na(+)/H(+) exchanger (NHE) isoforms are expressed in the stomach, and NHE1 and NHE2 knockout mice display gastric mucosal atrophy. This study investigated the cellular distribution of the NHE isoforms NHE1, NHE2, NHE3, and NHE4 in rabbit gastric epithelial cells and their regulation by intracellular pH (pH(i)), hyperosmolarity, and an increase in cAMP. Semiquantitative RT-PCR and Northern blot experiments showed high NHE1 and NHE2 mRNA levels in mucous cells and high NHE4 mRNA levels in parietal and chief cells. Fluorescence optical measurements in cultured rabbit parietal and mucous cells using the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein and NHE isoform-specific inhibitors demonstrated that in both cell types, intracellular acidification activates NHE1 and NHE2, whereas hyperosmolarity activates NHE1 and NHE4. The relative contribution of the different isoforms to pH(i)- and hyperosmolarity-activated Na(+)/H(+) exchange in the different cell types paralleled their relative expression levels. cAMP elevation also stimulated NHE4, whereas an increase in osmolarity above a certain threshold further increased NHE1 and not NHE4 activity. We conclude that in rabbit gastric epithelium, NHE1 and NHE4 regulate cell volume and NHE1 and NHE2 regulate pH(i). The high NHE1 and NHE2 expression levels in mucous cells may reflect their special need for pH(i) regulation during high gastric acidity. NHE4 is likely involved in volume regulation during acid secretion.

Trefoil Factor 2 Requires Na/H Exchanger 2 Activity to Enhance Mouse Gastric Epithelial Repair

“…3 and 4) but believe this unlikely to impact on the surface cell repair we measured. It should be noted that although we did not observe NHE2 immunostaining in gastric glands, others have reported NHE2 mRNA and transport activity in parietal cells (14,16). In our measures made at the gastric surface, a role for NHE2 transport activity is confirmed by the ability of HOE694 to block repair in response to exogenous trefoil peptide and is supported by the positive effect of HOE694 to block repair in wild-type mice.…”

A Reduction in Intestinal Cell pH Due to Loss of the Caenorhabditis elegans Na+/H+ Exchanger NHX-2 Increases Life Span

“…1-3). To date, eight electroneutral Na ϩ /H ϩ exchange (NHE) 1 family members have been identified in mammalian organisms, and several isoforms are expressed in the gastrointestinal tract (4). This class of protein has been implicated in cell volume regulation, net bicarbonate movement, and Na ϩ reabsorption and is thought to have a housekeeping role in maintaining pH homeostasis (5)(6)(7).…”

Identification and subcellular localization of the Na+/H+ exchanger and a novel related protein in the endocrine pancreas and adrenal medulla

“…NHE2 and NHE3 are mainly found at the apical pole of epithelial cells in kidney (Chambrey et al 1998), intestine (Chu et al 2002) and duct cells of salivary glands and pancreas (Lee et al 1998(Lee et al , 2000, where they play a role in Na C and fluid absorption, and secretion of protons (Orlowski & Grinstein 2004). NHE4 has been identified in the macula densa of the kidney (Peti-Peterdi et al 2000) and in the stomach (Rossmann et al 2001). NHE5 has mainly been found in the brain where it seems to behave like NHE3 (Baird et al 1999).…”