Seeing the light: calcium imaging in cells for drug discovery

Abstract Many ion channels and G protein-coupled receptors (GPCRs) alter the calcium concentration of mammalian cells on activation. To find functional ligands for these targets, high-throughput (HT) calcium assays are required to screen large chemical libraries. This review will compare fluorescent and luminescent imaging as technology platforms for developing HT calcium assays.

[1]  J. Northrop,et al.  Expression of cre recombinase as a reporter of signal transduction in mammalian cells. , 1999, Chemistry & biology.

[2]  R Y Tsien,et al.  Photochemically generated cytosolic calcium pulses and their detection by fluo-3. , 1989, The Journal of biological chemistry.

[3]  W. Sadee,et al.  Rapid measurements of intracellular calcium using a fluorescence plate reader. , 1999, BioTechniques.

[4]  E. B. Ridgway,et al.  Calcium transients in single muscle fibers. , 1967, Biochemical and biophysical research communications.

[5]  J. Kendall,et al.  Aequorea victoria bioluminescence moves into an exciting new era. , 1998, Trends in biotechnology.

[6]  G. Zlokarnik,et al.  Quantitation of transcription and clonal selection of single living cells with beta-lactamase as reporter. , 1998, Science.

[7]  M. Brini,et al.  Monitoring dynamic changes in free Ca2+ concentration in the endoplasmic reticulum of intact cells. , 1995, The EMBO journal.

[8]  R Y Tsien,et al.  Calcium channels, stores, and oscillations. , 1990, Annual review of cell biology.

[9]  S. Fraser,et al.  A Calcium-Sensitive Magnetic Resonance Imaging Contrast Agent , 1999 .

[10]  M. Greenberg,et al.  CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. , 1991, Science.

[11]  B. Neagle,et al.  FLIPR: A New Instrument for Accurate, High Throughput Optical Screening , 1996 .

[12]  Peter Lipp,et al.  Calcium - a life and death signal , 1998, Nature.

[13]  Christopher C. Goodnow,et al.  Differential activation of transcription factors induced by Ca2+ response amplitude and duration , 1997, Nature.

[14]  E Carafoli.  Intracellular calcium homeostasis. , 1987, Annual review of biochemistry.

[15]  P. Negulescu,et al.  Cell-based assays and instrumentation for screening ion-channel targets. , 1999, Drug discovery today.

[16]  R. Tsien,et al.  Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. , 1989, The Journal of biological chemistry.

[17]  S. Rees,et al.  A bioluminescent assay for agonist activity at potentially any G-protein-coupled receptor. , 1997, Analytical biochemistry.

[18]  Roger Y. Tsien,et al.  Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression , 1998, Nature.

[19]  R Marsault,et al.  Transfected Aequorin in the Measurement of Cytosolic Ca2+ Concentration ([Ca2+]c) , 1995, The Journal of Biological Chemistry.

[20]  R Marsault,et al.  Targeting aequorin and green fluorescent protein to intracellular organelles. , 1996, Gene.

[21]  T. Murphy,et al.  Induction of NFAT-mediated Transcription by G-coupled Receptors in Lymphoid and Non-lymphoid Cells (*) , 1996, The Journal of Biological Chemistry.

[22]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[23]  Martin D. Bootman,et al.  The elemental principles of calcium signaling , 1995, Cell.

[24]  P E Stanley,et al.  Chemiluminescent and bioluminescent reporter gene assays. , 1994, Analytical biochemistry.

[25]  P. Hogan,et al.  Transcription factors of the NFAT family: regulation and function. , 1997, Annual review of immunology.

[26]  Keli Xu,et al.  Calcium oscillations increase the efficiency and specificity of gene expression , 1998, Nature.