A multiplex calcium assay for identification of GPCR agonists and antagonists

Assay Drug Dev Technol. 2010 Jun;8(3):367-79. doi: 10.1089/adt.2009.0245.

Abstract

Activation of G(q) protein-coupled receptors can be monitored by measuring the increase in intracellular calcium with fluorescent dyes. Recent advances in fluorescent kinetic plate readers and liquid-handling technology have made it possible to follow these transient changes in intracellular calcium in a 1,536-well plate format for high-throughput screening (HTS). Here, we have applied the latest generation of fluorescence kinetic plate readers to multiplex the agonist and antagonist screens of a G protein-coupled receptor (GPCR). This multiplexed assay format provides an efficient and cost-effective method for HTS of G(q)-coupled GPCR targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Calcium / analysis
  • Calcium / metabolism*
  • Calibration
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Fluorescent Dyes
  • Indicators and Reagents
  • Kinetics
  • Muscarinic Agonists / pharmacology
  • Muscarinic Antagonists / pharmacology
  • Radioligand Assay
  • Receptor, Muscarinic M1 / drug effects
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*

Substances

  • Fluorescent Dyes
  • Indicators and Reagents
  • Muscarinic Agonists
  • Muscarinic Antagonists
  • NPSR1 protein, human
  • Receptor, Muscarinic M1
  • Receptors, G-Protein-Coupled
  • Cyclic AMP
  • Calcium