title: 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 Ca2+ levels indicating that it did not act via the recently described amino acid modulated Ca2+-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.
authors.affiliation: Institute of Physiology and Center for Integrative Human Physiology (CIHP), University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kirchhoff
authors.forename: Mital H
authors.initials: MH
authors.lastname: Dave
authors.forename: Christine
authors.initials: C
authors.lastname: Remy
authors.forename: Ortrud
authors.initials: O
authors.lastname: Kosiek
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Busque
authors.forename: Matthias
authors.initials: M
authors.lastname: Dufner
authors.forename: John P
authors.initials: JP
authors.lastname: Geibel
authors.forename: Francois
authors.initials: F
authors.lastname: Verrey
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
mesh_terms: D000200:Action Potentials; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000598:Amino Acids, Cyclic / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000502:physiology; D054328:Proton Pump Inhibitors; D011522:Protons; D051381:Rats; D017208:Rats, Wistar
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000598:Amino Acids, Cyclic; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D011522:Protons; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D002927:Cimetidine; D006632:Histamine; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D002118:Calcium