Presence of the NHE3 Isoform of the Na+/H+ Exchanger in Human Gallbladder

Abstract

1. In man and in various animal species, absorption of NaCl from bile by the gallbladder mucosa is associated with luminal proton secretion. A similar absorption of NaCl in small intestine, colon and renal tubule is related, at least in part, to the presence of the NHE3 isoform of the Na+/H+ exchanger. This work was designed to find out whether NHE3 is also present in human gallbladder. 2. At surgery, 100-200 mg of the gallbladder wall was obtained from patients treated by cholecystectomy for gallstones. After isolation of the mucosa, total RNA was extracted and submitted to reverse transcription-polymerase chain reaction with two primers: 5'-AAGCCICTGGTGCAGTGGCTGAAGG-3' and 5'-GGAGTCCTTIAAGTCGGCIAAGCTGGGC-3', designed to amplify a sequence of 645 bp of rabbit NHE3 mRNA (642 bp in man). RNA from human liver and from rabbit heart, neither of which contain NHE3, and human ileal RNA, which does contain NHE3, were used as controls. 3. RNA extracted from the mucosal moiety of the gallbladder wall gave an amplification product of about 645 nucleotides. Controls gave the expected negative or positive results. Sequencing of the amplified RNA showed it was almost identical to previously determined sequences of NHE3 in other human tissues. 4. It is concluded that the mucosa of human gallbladder contains the mRNA of NHE3 isoform. This isoform could therefore play a role in sodium absorption from bile.

Megalin and cubilin expression in gallbladder epithelium and regulation by bile acids

“…Thus, the correct acidification of alkaline hepatic bile in the gallbladder is a crucial event to prevent calcium precipitation and gallstone formation. Carbonic anhydrases (73) and NHE3 (7)(8)(9) are gallbladder proteins involved in the bile acidification mechanisms. In kidney proximal tubules, the activity of NHE3 is negatively regulated by megalin (27).…”

“…The formation of gallstones is also dependent on downstream events that occur in the gallbladder itself, including changes in the physicochemical properties of biliary lipids and gallbladder motility. For example, the gallbladder acts to concentrate bile through mechanisms that involve the adsorption of water and electrolytes (5,6), which are largely dependent upon Na ϩ /H ϩ exchange at the apical membrane of the gallbladder epithelium (GBE) (7)(8)(9). Gallstone formation is also related to an increase in gallbladder secretion of mucin, which correlates with the promotion of crystallization in experimental and human gallstone disease (10)(11)(12)(13).…”

Why should a clinician care about the molecular biology of transport?

“…These studies of NHE-knockout mice enhance our understanding of the physiologic role of epithelial isoforms of the Na + /H + exchangers. Still, further studies are needed to elucidate details of the role of these exchangers in humans, where they are present in the small intestine, colon [53,54], and gallbladder [55].…”

Estudo da região promotora do gene do permutador Na+/H+ (NHE3).

“…NHE3 é a forma mais abundante de permutador Na + /H + em tecido renal, mas é também expresso de forma abundante no trato intestinal, especialmente em íleo. É encontrado também nos demais segmentos do intestino delgado e em cólon (DONOWITZ e LI 2007), em vesícula biliar (COLOMBANI et al, 1996), epidídimo e várias regiões do cérebro (BRANT et al, 1995).…”