l -Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells
| Autor: | Karl L. Insogna, Jane E. Kerstetter, John P. Geibel, Stephanie M. Busque |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Physiology Phenylalanine chemistry.chemical_element Biology Calcium Divalent Gastric Acid Rats Sprague-Dawley H(+)-K(+)-Exchanging ATPase Mice Parietal Cells Gastric Physiology (medical) Gastric glands medicine Animals Secretion Amino Acids Receptor chemistry.chemical_classification Dose-Response Relationship Drug Hepatology Tryptophan Gastroenterology Gastric Acidity Determination Anti-Ulcer Agents Stimulation Chemical Rats Amino acid medicine.anatomical_structure Biochemistry chemistry Gastric acid Calcium-sensing receptor Cimetidine Receptors Calcium-Sensing Omeprazole |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 289:G664-G669 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00096.2005 |
| Popis: | Parietal cells are the primary acid secretory cells of the stomach. We have previously shown that activation of the calcium-sensing receptor (CaSR) by divalent (Ca2+) or trivalent (Gd3+) ions stimulates acid production in the absence of secretagogues by increasing H+,K+-ATPase activity. When overexpressed in HEK-293 cells, the CaSR can be allosterically activated by l-amino acids in the presence of physiological concentrations of extracellular Ca2+ (Cao2+; 1.5–2.5 mM). To determine whether the endogenously expressed parietal cell CaSR is allosterically activated by l-amino acids, we examined the effect of the amino acids l-phenylalanine (l-Phe), l-tryptophan, and l-leucine on acid secretion. In ex vivo whole stomach preparations, exposure to l-Phe resulted in gastric luminal pH significantly lower than controls. Studies using d-Phe (inactive isomer) failed to elicit a response on gastric pH. H+-K+-ATPase activity was monitored by measuring the intracellular pH (pHi) of individual parietal cells in isolated rat gastric glands and calculating the rate of H+ extrusion. We demonstrated that increasing Cao2+ in the absence of secretagogues caused a dose-dependent increase in H+ extrusion. These effects were amplified by the addition of amino acids at various Cao2+ concentrations. Blocking the histamine-2 receptor with cimetidine or inhibiting system l-amino acid transport with 2-amino-2-norbornane-carboxylic acid did not affect the rate of H+ extrusion in the presence of l-Phe. These data support the conclusion that amino acids, in conjunction with a physiological Cao2+ concentration, can induce acid secretion independent of hormonal stimulation via allosteric activation of the stomach CaSR. |
| Databáze: | OpenAIRE |
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