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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kupferman, I. A. Rev. Neurosci. 2, 447–465 (1979).
Drummond, G. I. Adv. Cyclic Nucleotide Res. 15, 373–494 (1983).
Sutherland, E. W. & Rall, T. W. Pharmac. Rev. 12, 265–299 (1960).
Sutherland, E. W. & Robison, G. A. Pharmac. Rev. 18, 145–161 (1966).
Patchornik, A., Amit, B. & Woodward, R. B. J. Am. chem. Soc. 92, 6333–6335 (1970).
Nargeot, J., Nerbonne, J. M., Engels, J. & Lester, H. A. Proc. natn. Acad. Sci. U.S.A. 80, 2395–2399 (1983).
Engels, J. & Schlaeger, E. J. J. med. Chem. 20, 907–911 (1977).
Lester, H. A. & Nerbonne, J. M. A. Rev. Biophys. Bioengng 11, 151–175 (1982).
Nargeot, J. et al. J. gen. Physiol. 79, 657–678 (1982).
Kaplan, J. H., Forbush, B. & Hoffmann, J. F. Biochemistry 17, 1929–1935 (1978).
McCray, J. A., Herbette, L., Kihara, T. & Trentham, D.R. Proc. natn. Acad. Sci. U.S.A. 77, 7327–7341 (1980).
Reuter, H. A. A. Rev. Physiol. 41, 413–424 (1979).
Reuter, H. A. Nature 301, 569–574 (1983).
Tsien, R. W. A. Rev. Physiol. 45, 341–358 (1983).
Schlossmann, V. K. Arzneimittel-Forsch. 22, 60–62 (1972).
Morad, M., Goldman, T. E. & Trentham, D. R. Nature 304, 635–638 (1983).
Nerbonne, J. M., Richard, S. & Nargeot, J. (in preparation).
Trautwein, W., Taniguchi, J. & Noma, A. Pflügers Arch. ges. Physiol. 392, 307–314 (1982).
Cachelin, A. B., dePeyer, J. E., Kokubun, S. & Reuter, H. Nature 304, 462–464 (1983).
Bean, B. P., Nowycky, M. C. & Tsien, R. W. Nature 307, 371–375 (1984).
Garnier, D., Lester, H. A., Nargeot, J., Nerbonne, J. M. & Richard, S. J. Physiol., Lond. 344, 38P (1983).
Engels, J. & Reidys, R. Experientia 34, 14–15 (1978).
Fetscher, C. A. Org. Syn. Coll. 4, 735–737 (1963).
Davies, H. W. & Schwarz, M. J. org. Chem. 30, 1242–1244 (1965).
Ried, W. & Ritz, M. Justus Liebigs Annln Chem. 691, 50–54 (1966).
Richard, S., Nerbonne, J. M., Nargeot, J. & Garnier, D. Pflügers Arch. ges. Physiol (submitted).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/310074a0
This article is cited by
-
The nitrodibenzofuran chromophore: a new caging group for ultra-efficient photolysis in living cells
Nature Methods (2006)
-
Photochemical tools for remote control of ion channels in excitable cells
Nature Chemical Biology (2005)
-
Insulin disrupts β-adrenergic signalling to protein kinase A in adipocytes
Nature (2005)
-
Mechanism of odorant adaptation in the olfactory receptor cell
Nature (1997)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
