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

Steven H. Young, Enrique Rozengurt


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


  • E. Rozengurt is the Ronald S. Hirshberg Professor of Translational Pancreatic Cancer Research.

  • Address for reprint requests and other correspondence: E. Rozengurt, 900 Veteran Ave., Warren Hall Rm. 11-124, Dept. of Medicine, School of Medicine, Univ. of California, Los Angeles, CA 90095-1786 (E-mail: erozengurt{at}

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • First published February 6, 2002;10.1152/ajpcell.00432.2001

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