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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

Copper inhibits P2Y(2)-dependent Ca(2+) signaling through the effects on thapsigargin-sensitive Ca(2+) stores in HTC

Svjetlana Dolovcak1, Shar L Waldrop, J Gregory Fitz

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9151, USA.

Biochemical and Biophysical Research Communications
|June 3, 2010
PubMed

Insights

Copper inhibits purinergic P2Y(2) receptors in liver cells by affecting calcium stores. This extracellular action may impair liver cell volume regulation, particularly in conditions with high serum copper.

Area of Science:

  • Hepatology and cell signaling research.
  • Investigating G-protein coupled receptors and ion channel regulation.
  • Exploring the role of trace elements in liver physiology.

Background:

  • Purinergic P2Y(2) receptors are crucial for hepatic calcium (Ca2+) signaling, responding to extracellular ATP.
  • Elevated serum copper levels occur in certain liver diseases, prompting investigation into copper's cellular effects.
  • Understanding copper's impact on liver cell function is vital for disease management.

Purpose of the Study:

  • To determine the effects of copper on P2Y(2) receptors in a liver cell model.
  • To elucidate the mechanism by which copper interacts with hepatic purinergic signaling.
  • To assess copper's influence on liver cell volume regulation.

Main Methods:

  • Utilized a model liver cell line (HTC cells) for experimental studies.
  • Administered P2Y(2) receptor agonist (UTP) and thapsigargin to assess calcium release.
  • Quantified intracellular calcium ([Ca2+]i) changes and cell viability following copper exposure.
  • Investigated copper's extracellular action and concentration-dependent inhibition (IC50).

Main Results:

  • Copper exposure inhibited UTP- and thapsigargin-evoked increases in intracellular calcium.
  • Copper acted extracellularly, without entering the cytosol, with an IC50 of approximately 15µM.
  • Copper inhibited P2Y(2) receptor-mediated calcium release from thapsigargin-sensitive stores.
  • Copper exposure impaired regulatory volume decrease (RVD) in response to hypotonic solutions.

Conclusions:

  • Copper potently inhibits hepatic P2Y(2) receptors and calcium signaling by acting extracellularly on calcium stores.
  • Copper-induced disruption of purinergic signaling and calcium homeostasis may contribute to liver dysfunction in hypercupremia.
  • These findings highlight a potential mechanism linking elevated copper levels to impaired liver cell volume regulation.

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