Amino acids and Ca2+ stimulate different patterns of Ca2+ oscillations through the Ca2+-sensing receptor.
We determined the effect of aromatic amino acid stimulation of the human extracellular Ca2+-sensing receptor (CaR) on intracellular Ca2+ concentration ([Ca2+]i) in single HEK-293 cells. Addition of L-phenylalanine or L-tryptophan (at 5 mM) induced [Ca2+]i oscillations from a resting state that was quiescent at 1.8 mM extracellular Ca2+ concentration ([Ca2+]e). Each [Ca2+]i peak returned to baseline values, and the average oscillation frequency was approximately 1 min(-1) at 37 degrees C. Oscillations were not induced or sustained if the [Ca2+]e was reduced to 0.5 mM, even in the continued presence of amino acid. Average oscillation frequency in response to an increase in [Ca2+]e (from 1.8 to 2.5-5 mM) was much higher (approximately 4 min(-1)) than that induced by aromatic amino acids. Oscillations in response to [Ca2+]e were sinusoidal whereas those induced by amino acids were transient. Thus both amino acids and Ca2+, acting through the same CaR, produce oscillatory increases in [Ca2+]i, but the resultant oscillation pattern and frequency allow the cell to discriminate which agonist is bound to the receptor.
Young
Steven H
SH
Unit of Signal Transduction and Gastrointestinal Cancer, Division of Digestive Diseases, Department of Medicine, School of Medicine, University of California, Los Angeles, California 90095-1786, USA.
Rozengurt
Enrique
E
D000596:Amino Acids / Q000494:pharmacology*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007424:Intracellular Fluid / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010649:Phenylalanine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D014162:Transfection; D014364:Tryptophan / Q000494:pharmacology
D000596:Amino Acids; D001896:Boron Compounds; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C049925:fura-2-am; D010649:Phenylalanine; D014364:Tryptophan; C109986:2-aminoethoxydiphenyl borate; D011493:Protein Kinase C; D002118:Calcium; D016257:Fura-2