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Am J Physiol Cell Physiol 282: C1414-C1422, 2002. First published February 6, 2002; doi:10.1152/ajpcell.00432.2001
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Vol. 282, Issue 6, C1414-C1422, June 2002

Amino acids and Ca2+ stimulate different patterns of Ca2+ oscillations through the Ca2+-sensing receptor

Steven H. Young and Enrique Rozengurt

Unit of Signal Transduction and Gastrointestinal Cancer, Division of Digestive Diseases, Department of Medicine, School of Medicine; and UCLA-CURE Digestive Diseases Research Center and Molecular Biology Institute, University of California, Los Angeles, California 90095-1786

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 ~1 min-1 at 37°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 (~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.

sinusoidal calcium oscillations; baseline calcium oscillations; allosteric; G protein-coupled receptors


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