An amino acid transporter involved in gastric acid secretion

Abstract

Gastric acid secretion is regulated by a variety of stimuli, in particular histamine and acetyl choline. In addition, dietary factors such as the acute intake of a protein-rich diet and the subsequent increase in serum amino acids can stimulate gastric acid secretion only through partially characterized pathways. Recently, we described in mouse stomach parietal cells the expression of the system L heteromeric amino acid transporter comprised of the LAT2-4F2hc dimer. Here we address the potential role of the system L amino acid transporter in gastric acid secretion by parietal cells in freshly isolated rat gastric glands. RT-PCR, western blotting and immunohistochemistry confirmed the expression of 4F2-LAT2 amino acid transporters in rat parietal cells. In addition, mRNA was detected for the B 0 AT1, ASCT2, and ATB(0+) amino acid transporters. Intracellular pH measurements in parietal cells showed histamine-induced and omeprazole-sensitive H + -extrusion which was enhanced by about 50% in the presence of glutamine or cysteine (1 mM), two substrates of system L amino acid transporters. BCH, a non-metabolizable substrate and a competitive inhibitor of system L amino acid transport, abolished the stimulation of acid secretion by glutamine or cysteine suggesting that this stimulation required the uptake of amino acids by system L. In the absence of histamine glutamine also stimulated H + -extrusion, whereas glutamate did not. Also, phenylalanine was effective in stimulating H + /K + -ATPase activity. Glutamine did not increase intracellular Ca 2+ levels indicating that it did not act via the recently described amino acid modulated Ca 2+ -sensing receptor. These data suggest a novel role for heterodimeric amino acid transporters and may elucidate a pathway by which protein-rich diets stimulate gastric acid secretion.

The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands

“…Blockade of H2 histamine receptors with cimetidine (100 M) did not influence the Gd 3ϩ -stimulated pH recovery, ruling out the involvement of histamine in the effect on H ϩ -K ϩ -ATPase activity (n ϭ 34 cells from 4 glands from 2 patients). ity in isolated rat gastric glands by a dual mechanism (1,12). At low concentrations, this appears to involve the uptake of amino acids by amino acid transporters, whereas at higher concentrations, the CaSR appears to be involved (1,12).…”

“…ity in isolated rat gastric glands by a dual mechanism (1,12). At low concentrations, this appears to involve the uptake of amino acids by amino acid transporters, whereas at higher concentrations, the CaSR appears to be involved (1,12). Thus, under these conditions, the CaSR could be acting as a metabolic sensor through which several metabolic pathways could modulate gastric acid secretion (11).…”

Taste Receptors in the Gastrointestinal Tract II.l-Amino acid sensing by calcium-sensing receptors: implications for GI physiology

“…In addition, it has been shown recently that the CaR-active amino acids, L-Phe and L-Trp, stimulate acid secretion from isolated gastric glands in a manner that is highly dependent on variations in the Ca 2ϩ o between 1.0 and 2.0 mM, behavior that is typical of the CaR (10). Although the system L-amino acid transporter may also contribute to amino acid-induced activation of gastric acid secretion (30), the specific inhibitor 2-amino-2-norbornanecarboxylic acid did not block these effects of L-Phe or L-Trp (10).…”

“…Both amino acids (AAs) and Ca 2ϩ ions are depicted as activators of the CaR. A putative alternative mechanism for the action of amino acids on acid secretion via the system L-transporter is also shown (30). ECL, enterochromaffin-like cells.…”

Nutraceuticals as Chemopreventive and Therapeutic agents in Gut Associated Pathogenesis

“…The concentration of glutamate in blood is reported to be lowest because most of the glutamate is absorbed and consumed by GI epithelium during transcellullar transport from the gut lumen [64]. Large number of transporter molecules are expressed in epithelial cells of gastric lining but only few of them are involved in glutamate transport system [65,66]. Glutamate activates contractile action in the gastric fundus possibly via cholinergic neurons [58, 59,67].…”