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

Nerbonne, Jeanne M. and Richard, Sylvain and Nargeot, Joel and Lester, Henry A. (1984) New photoactivatable cyclic nucleotides produce intracellular jumps in cyclic AMP and cyclic GMP concentrations. Nature, 310 (5972). pp. 74-76. ISSN 0028-0836. doi:10.1038/310074a0. https://resolver.caltech.edu/CaltechAUTHORS:20201012-160322096

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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 scales. Despite the widespread acceptance of this second messenger mechanism 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, substituted 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 previously. 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.


Item Type:Article
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URLURL TypeDescription
https://doi.org/10.1038/310074a0DOIArticle
https://rdcu.be/b8p1BPublisherFree ReadCube access
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1984 Nature Publishing Group. Received 31 January; accepted 12 April 1984. We thank Roger Spencer for assistance with the HPLC experiments and David Trentham for helpful discussions. This research was supported by the NIH (grant GM-29836), by INSERM, France (grant 835012) and by the American Heart Association (Postdoctoral Fellowship to J.M.N.). We also thank Centre d'etudes et de Recherches Servier, Neuilly/Seine (France) for a travel grant to J.M.N.
Funders:
Funding AgencyGrant Number
NIHGM-29836
Institut national de la santé et de la recherche médicale (INSERM)835012
American Heart AssociationUNSPECIFIED
Laboratoire ServierUNSPECIFIED
Issue or Number:5972
DOI:10.1038/310074a0
Record Number:CaltechAUTHORS:20201012-160322096
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201012-160322096
Official Citation: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
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106000
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:13 Oct 2020 14:25
Last Modified:16 Nov 2021 18:48

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