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New photoactivatable cyclic nucleotides produce intracellular jumps in cyclic AMP and cyclic GMP concentrations

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Abstract

The cyclic nucleotides cyclic AMP and cyclic GMP are important intracellular messengers mediating the responses to neurotransmitters and neurohormones and regulating cellular function over a wide range of time scales1,2. Despite the widespread acceptance of this second messenger mechanism3,4 in many systems, much remains unknown about their mechanism of action, except that such events are associated with increases or decreases in intracellular cyclic nucleotides. Quantitative descriptions of cyclic nucleotide-dependent processes are hampered by the absence of a means by which intracellular cyclic nucleotide concentrations can be accurately controlled. We have now designed, synthesized and characterized new, substituted5 photolabile cyclic nucleotide analogues, the 4,5-dimethoxy-2-nitrobenzyl esters of cyclic AMP and cyclic GMP (Fig. 1), which are physiologically inert before irradiation and which liberate free cyclic AMP or cyclic GMP on absorption of a photon. The thermal properties and photolysis rates and efficiencies of light-induced release of cyclic nucleotides from these analogues are more favourable than for the simple o-nitrobenzyl derivatives used previously6. These molecules should permit intracellular ‘concentration jumps’ of cyclic AMP or cyclic GMP to be produced in cells under physiological investigation with spatial and temporal resolution unmatched by conventional techniques.

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Authors and Affiliations

  1. Division of Biology, 156–29, California Institute of Technology, Pasadena, California, 91125, USA

    Jeanne M. Nerbonne & Henry A. Lester

  2. Laboratoire d'Électrophysiologie et de Pharmacologie Cellulaires, Université Francois Rabelais, 37200, Tours, France

    Sylvain Richard & Joel Nargeot

Authors
  1. Jeanne M. Nerbonne
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  2. Sylvain Richard
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  3. Joel Nargeot
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  4. Henry A. Lester
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Nerbonne, J., Richard, S., Nargeot, J. et al. New photoactivatable cyclic nucleotides produce intracellular jumps in cyclic AMP and cyclic GMP concentrations. Nature 310, 74–76 (1984). https://doi.org/10.1038/310074a0

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