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. 1992 Sep 15;89(18):8586–8590. doi: 10.1073/pnas.89.18.8586

Adenosine decreases neurotransmitter release at central synapses.

D A Prince 1, C F Stevens 1
PMCID: PMC49965  PMID: 1382294

Abstract

Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy of transmission at the perforant path synapses on dentate granule cells. We have used whole cell recording from these cells in slices to determine the mechanism of the reduced synaptic strength. We find that size of miniature excitatory postsynaptic currents (mepscs) is unaffected by adenosine at concentrations up to 100 microM, an observation that indicates adenosine's mode of action is not through a decreased postsynaptic sensitivity to neurotransmitter. A quantal analysis indicates, however, that the quantity of neurotransmitter released is sufficiently diminished by adenosine to account entirely for the adenosine-produced decrease in synaptic strength. Application of 3-isobutyl-1-methylxanthine (IBMX), a drug that antagonizes the effects of endogenous adenosine, produces an increase in synaptic strength. This observation suggests that the resting level of adenosine in our slices is appreciable, and an analysis of the adenosine dose-response relation is consistent with endogenous adenosine levels of about 10 microM. IBMX application produces only slight changes in the amplitude of mepscs, whereas a quantal analysis demonstrates that the drug significantly increases the amount of neurotransmitter released. Thus IBMX acts as an "anti-adenosine" in our experiments. In some experiments we have been able to record excitatory and inhibitory synaptic currents produced by the same perforant path stimulus. In these instances we find that inhibitory transmission is unaffected by concentrations of adenosine that produce a marked decrease in the strength of excitatory synapses.

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Selected References

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  1. Aghajanian G. K., Rasmussen K. Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices. Synapse. 1989;3(4):331–338. doi: 10.1002/syn.890030406. [DOI] [PubMed] [Google Scholar]
  2. Bekkers J. M., Richerson G. B., Stevens C. F. Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5359–5362. doi: 10.1073/pnas.87.14.5359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bekkers J. M., Stevens C. F. NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus. Nature. 1989 Sep 21;341(6239):230–233. doi: 10.1038/341230a0. [DOI] [PubMed] [Google Scholar]
  4. Brănişteanu D. D., Haulică I. D., Proca B., Nhue B. G. Adenosine effects upon transmitter release parameters in the Mg2+-paralyzed neuro-muscular junction of frog. Naunyn Schmiedebergs Arch Pharmacol. 1979 Sep;308(3):273–279. doi: 10.1007/BF00501393. [DOI] [PubMed] [Google Scholar]
  5. Chavez-Noriega L. E., Stevens C. F. Modulation of synaptic efficacy in field CA1 of the rat hippocampus by forskolin. Brain Res. 1992 Mar 6;574(1-2):85–92. doi: 10.1016/0006-8993(92)90803-h. [DOI] [PubMed] [Google Scholar]
  6. DEL CASTILLO J., KATZ B. Statistical factors involved in neuromuscular facilitation and depression. J Physiol. 1954 Jun 28;124(3):574–585. doi: 10.1113/jphysiol.1954.sp005130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dunwiddie T. V. The physiological role of adenosine in the central nervous system. Int Rev Neurobiol. 1985;27:63–139. doi: 10.1016/s0074-7742(08)60556-5. [DOI] [PubMed] [Google Scholar]
  8. Dunwiddie T. V., Worth T. Sedative and anticonvulsant effects of adenosine analogs in mouse and rat. J Pharmacol Exp Ther. 1982 Jan;220(1):70–76. [PubMed] [Google Scholar]
  9. Ginsborg B. L., Hirst G. D. The effect of adenosine on the release of the transmitter from the phrenic nerve of the rat. J Physiol. 1972 Aug;224(3):629–645. doi: 10.1113/jphysiol.1972.sp009916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Greene R. W., Haas H. L. The electrophysiology of adenosine in the mammalian central nervous system. Prog Neurobiol. 1991;36(4):329–341. doi: 10.1016/0301-0082(91)90005-l. [DOI] [PubMed] [Google Scholar]
  11. Greengard P., Jen J., Nairn A. C., Stevens C. F. Enhancement of the glutamate response by cAMP-dependent protein kinase in hippocampal neurons. Science. 1991 Sep 6;253(5024):1135–1138. doi: 10.1126/science.1716001. [DOI] [PubMed] [Google Scholar]
  12. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  13. Knapp A. G., Dowling J. E. Dopamine enhances excitatory amino acid-gated conductances in cultured retinal horizontal cells. 1987 Jan 29-Feb 4Nature. 325(6103):437–439. doi: 10.1038/325437a0. [DOI] [PubMed] [Google Scholar]
  14. Knapp A. G., Schmidt K. F., Dowling J. E. Dopamine modulates the kinetics of ion channels gated by excitatory amino acids in retinal horizontal cells. Proc Natl Acad Sci U S A. 1990 Jan;87(2):767–771. doi: 10.1073/pnas.87.2.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lambert N. A., Teyler T. J. Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus. Neurosci Lett. 1991 Jan 14;122(1):50–52. doi: 10.1016/0304-3940(91)90190-5. [DOI] [PubMed] [Google Scholar]
  16. MacDonald R. L., Skerritt J. H., Werz M. A. Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture. J Physiol. 1986 Jan;370:75–90. doi: 10.1113/jphysiol.1986.sp015923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Phillis J. W., Wu P. H. The role of adenosine and its nucleotides in central synaptic transmission. Prog Neurobiol. 1981;16(3-4):187–239. doi: 10.1016/0301-0082(81)90014-9. [DOI] [PubMed] [Google Scholar]
  18. Ribeiro J. A., Walker J. The effects of adenosine triphosphate and adenosine diphosphate on transmission at the rat and frog neuromuscular junctions. Br J Pharmacol. 1975 Jun;54(2):213–218. doi: 10.1111/j.1476-5381.1975.tb06931.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Silinsky E. M. On the mechanism by which adenosine receptor activation inhibits the release of acetylcholine from motor nerve endings. J Physiol. 1984 Jan;346:243–256. doi: 10.1113/jphysiol.1984.sp015019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smellie F. W., Davis C. W., Daly J. W., Wells J. N. Alkylxanthines: inhibition of adenosine-elicited accumulation of cyclic AMP in brain slices and of brain phosphodiesterase activity. Life Sci. 1979 Jun 25;24(26):2475–2482. doi: 10.1016/0024-3205(79)90458-2. [DOI] [PubMed] [Google Scholar]
  21. Stiles G. L. Adenosine receptors. J Biol Chem. 1992 Apr 5;267(10):6451–6454. [PubMed] [Google Scholar]
  22. Trussell L. O., Jackson M. B. Adenosine-activated potassium conductance in cultured striatal neurons. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4857–4861. doi: 10.1073/pnas.82.14.4857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wang L. Y., Salter M. W., MacDonald J. F. Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases. Science. 1991 Sep 6;253(5024):1132–1135. doi: 10.1126/science.1653455. [DOI] [PubMed] [Google Scholar]
  24. Yoon K. W., Rothman S. M. Adenosine inhibits excitatory but not inhibitory synaptic transmission in the hippocampus. J Neurosci. 1991 May;11(5):1375–1380. doi: 10.1523/JNEUROSCI.11-05-01375.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. van Calker D., Müller M., Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem. 1979 Nov;33(5):999–1005. doi: 10.1111/j.1471-4159.1979.tb05236.x. [DOI] [PubMed] [Google Scholar]

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