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pH Sensing by the calcium-sensing receptor.

Stephen J Quinn1, Mei Bai, Edward M Brown

  • 1Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA. squinn@rics.bwh.harvard.edu

The Journal of Biological Chemistry
|June 18, 2004
PubMed
Summary

Extracellular pH significantly modulates the calcium-sensing receptor (CaR) activity, affecting its sensitivity to calcium and other agonists. This pH-dependent regulation is crucial for CaR function in various tissues, including the brain and kidney.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • The calcium-sensing receptor (CaR) regulates serum calcium levels by sensing extracellular calcium (Ca(o)).
  • CaR is activated by polycationic molecules, suggesting electrostatic interactions are key to its function.
  • The influence of extracellular pH on CaR activity and its agonists has not been fully elucidated.

Purpose of the Study:

  • To investigate how extracellular pH modulates the activation of the calcium-sensing receptor (CaR) by various agonists.
  • To determine if changes in extracellular pH affect CaR sensitivity to calcium and other endogenous modulators.
  • To explore the potential role of CaR as a pH sensor in different physiological contexts.

Main Methods:

  • Utilized human embryonic kidney 293 cells expressing CaR.

Related Experiment Videos

  • Assessed CaR activation by calcium and other agonists across a range of extracellular pH values.
  • Investigated the impact of altered extracellular pH on CaR sensitivity and compared it with other G-protein-coupled receptors.
  • Main Results:

    • Extracellular pH significantly altered CaR activation by Ca(o) and other agonists.
    • Increased pH enhanced CaR sensitivity to agonists, while decreased pH reduced it.
    • Intracellular pH changes did not account for the observed effects; extracellular pH directly impacts CaR.

    Conclusions:

    • Extracellular pH is a critical modulator of calcium-sensing receptor (CaR) activity.
    • CaR exhibits altered sensitivity to agonists with deviations in pH, suggesting a direct interaction.
    • CaR may function as a sensor for pH and acid-base status in tissues like the stomach, kidney, bone, and brain.