Abstract
Adenosine and its analogues are potent inhibitors of synaptic activity in the central and peripheral nervous system1,2. In the central nervous system (CNS), this appears to arise primarily by inhibition of presynaptic release of transmitters3,4, including glutamate5, which is possibly the major excitatory transmitter in the brain. In addition, postsynaptic effects of adenosine have been reported which would also serve to reduce neurotransmission6,7. The mechanism by which adenosine inhibits CNS neurotransmission is unknown, although it appears to exert its effect via an A1 receptor2,8 which in some systems is negatively coupled to adenylate cyclase9. In an attempt to elucidate the mechanism of inhibition, we have examined the effect of pertussis toxin (PTX) on the ability of the stable adenosine analogue (−)phenylisopropy-ladenosine (PIA) to inhibit glutamate release from cerebellar neurones maintained in primary culture. PTX, by ADP-ribosy-lating the nucleotide-binding protein Ni, prevents coupling of inhibitory receptors such as the A1 receptor to adenylate cyclase10. As reported here, we found that PTX, as well as preventing inhibition of adenylate cyclase by PIA, also converts the PIA-induced inhibition of glutamate release to a stimulation. Our results suggest strongly that purinergic inhibitory modulation of transmitter release occurs by inhibition of adenylate cyclase.
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References
Schubert, P. & Mitzdorf, U. Brain Res. 172, 186–190 (1979).
Dunwiddie, T. V. & Hoffer, B. Br. J. Pharmac. 69, 59–68 (1980).
Vizi, E. S. & Knoll, J. Neuroscience 1, 391–398 (1976).
Fredholm, B. B. & Hedqvist, P. Biochem. Pharmac. 29, 1635–1643 (1980).
Dolphin, A. C. & Archer, E. R. Neurosci. Lett. 43, 49–54 (1983).
Segal, M. Eur. J. Pharmac. 79, 193–199 (1982).
Proctor, W. R. & Dunwiddie, T. V. Neurosci. Lett. 35, 197–201 (1983).
Reddington, M., Lee, K. S. & Schubert, P. Neurosci. Lett. 28, 275–279 (1982).
Van Calker, D., Muller, M. & Hamprecht, B. J. Neurochem. 33, 999–1005 (1979).
Katada, T. & Ui, M. Proc. natn. Acad. Sci., U.S.A. 79, 3129–3133 (1982).
Gallo, V., Ciotti, M. T., Coletti, A., Aloisi, F. & Levi, G. Proc. natn. Acad. Sci. U.S.A. 79, 7919–7923 (1982).
Pearce, B. R. et al. J. Neurosci. Meth. 3, 255–259 (1981).
Wojcik, W. J. & Neff, N. J. Neurochem. 41, 759–763 (1983).
Katada, T., Northup, J. K., Bokoch, G. M. Ui, M. & Gilman, A. G. J. biol Chem. 259, 3578–3585 (1984).
Spignoli, G., Pedata, F. & Pepeu, G. Eur. J. Pharmac. 97, 341–342 (1984).
Wu, P. H., Phillis, J. W. & Thierry, D. L. J. Neurochem. 39, 700–708 (1982).
Halliwell, J. V. & Scholfield, C. N. Neurosci Lett. 50, 13–18 (1984).
Kuroda, Y. in Proc. int. Workshop on Adenosine and Xanthine Derivatives (eds Schubert, P., Stefanovich, V. & Rudolphi, K.) (IRL, Oxford, in the press).
Dolphin, A. C., Forda, S. R. & Scott, R. H. J. Physiol, Lond. (in the press).
Boyer, J. L., Garcia, A., Posadas, C. & Garcia-Saintz, J. A. J. biol Chem. 259, 8076–8079 (1984).
Hughes, A. R., Martin, M. W. & Harden, T. K. Proc. natn. Acad. Sci U.S.A. 81, 5680–5684 (1984).
Nakamura, T. & Ui, M. FEBS Lett. 173, 414–418 (1984).
Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).
Tucker, J. F. Br. J. Pharmac. 83, 326–328 (1984).
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Dolphin, A., Prestwich, S. Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Nature 316, 148–150 (1985). https://doi.org/10.1038/316148a0
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DOI: https://doi.org/10.1038/316148a0
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