The Sources of Extracellular Adenosine in Hippocampus and Neostriatum of the Rat Brain


Endogenous adenosine can enter the extracellular space either by direct release or via formation from adenine nucleotides. We have compared the effects of substances blocking the ecto-5'-nucleotidase with a, b-methylene adenosine 5'-diphosphate (AOPCP) or adenosine kinase with iodotubercidin (Itu) on field potentials in the hippocampus and the neostriatum in vitro evoked by stimulation of the stratum radiatum or the cortico-striatal pathway respectively. AOPCP enhanced the amplitude of the population spikes by 34% in the hippocampus and by 26.5% in the neostriatum. DPCPX, a selective A1-receptor antagonist, increased the amplitude of the population spikes by 68% in the hippocampus and by 53.5% in the neostriatum. Thus both, release of adenosine from the intracellular space and, extracellular dephosphorylation of adenine nucleotides to a lesser extent, contribute to the effective levels of adenosine in the extracellular space in hippocampus and neostriatum.

Share and Cite:

Pak, M. and Yetkin, Y. (2014) The Sources of Extracellular Adenosine in Hippocampus and Neostriatum of the Rat Brain. World Journal of Neuroscience, 4, 85-91. doi: 10.4236/wjns.2014.42010.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Kase, H., Richardsonand, P.J. and Jenner, P. (2000) Adenosin Receptors and Parkinson Disease. Academic Press, London.
[2] Bruns, R.F., Fergus, J.H., Badger, E.V., Bristol, J.A., Santay, L.A., Hartman, J.D., Hays, S.J. and Huang, C.C. (1987) Binding of the A1 Selective Adenosine Antagonist 8-Cyclopentyl-1,3-dipropylxanthine to Rat Brain Membranes. NaunynSchmiedeberg’s Archives of Pharmacology, 335, 59-63.
[3] Gerber, U., Greene, R.W., Haas, H.L. and Stevens, D.R. (1989) Characterization of Inhibition Mediated by Adenosine in the Hippocampus of the Rat in Vitro. The Journal of Physiology, 417, 567-578.
[4] Thompson, S.M., Haas, H.L. and Gahwiler, B.H. (1992) Comparison of the Actions of Adenosine at Preand Postsynaptic Receptors in the Rat Hippocampus in Vitro. The Journal of Physiology, 451, 347-363.
[5] Fastbom, J. and Fredholm, B.B. (1985) Inhibition of [3H] Glutamate Release from Rat Hippocampal Slices by Lphenylisopropyladenosine. Acta Physiologica, 125, 121-123.
[6] Dunwiddie, T.V. (1985) The Physiological Role of Adenosine in the Central Nervous System. International Review of Neurobiology, 27, 63-139.
[7] Huston, J.P., Haas, H.L., Boix, F., Pfister, M., Decking, U., Schrader, J. and Schwarting, R.K. (1996) Extracellular Adenosine Levels in Neostriatum and Hippocampus during Rest and Activity Periods of Rats. Neuroscience, 73, 99-107.
[8] Winn, H.R., Rubio, R. and Berne, R.M. (1981) Brain Adenosine Concentration during Hypoxia in Rats. American Journal of Physiology, 241, 235-242.
[9] Chao, D. and Xia, Y. (2010) Ionic Storm in Hypoxic/Ischemic Stress: Can Opioid Receptors Subside It Progress in Neurobiology, 90, 439-470.
[10] During, M.J. and Spencer, D.D. (1992) Adenosine: A Potential Mediator of Seizure Arrest and Postictal Refractoriness. Annals of Neurology, 32, 618-624.
[11] Deckert, J., Morgan, P.F. and Marangos, P.J. (1988) Adenosine Uptake Site Heterogeneity in the Mammalian CNS Uptake Inhibitors as Probes and Potential Neuropharmaceuticals. Life Sciences, 42, 1331-1345.
[12] Lee, C.W. and Jarvis, S.M. (1988) Nucleoside Transport in Rat Cerebral-Cortical Synaptosomes. Evidence for Two Types of Nucleoside Transporters. Biochemical Journal, 249, 557-564.
[13] Richardson, P.J., Brown, S.J., Bailyes, E.M. and Luzio, J.P. (1987) Ectoenzymes Control Adenosine Modulation of Immunoisolated Cholinergic Synapses. Nature, 327, 232-234.
[14] Zimmermann, H., Vogel, M. and Laube, U. (1993) Hippocampal Localization of 5'-Nucleotidase as Revealed by Immunocytochemistry. Neuroscience, 55, 105-112.
[15] Magalhes-Cardoso, M.T., Pereira, M.F., Oliveira, L., Ribeiro, J.A., Cunha, R.A. and Correia-de-Sá, P. (2003) EctoAMP Deaminase Blunts the ATP-Derived Adenosine A2A Receptor Facilitation of Acetylcholine Release at Rat Motor Nerve Endings. The Journal of Physiology, 549, 399-408.
[16] Lloyd, H.G., Lindstrom, K. and Fredholm, B.B. (1993) Intracellular Formation and Release of Adenosine from Rat Hippocampal Slices Evoked by Electrical Stimulation or Energy Depletion. Neurochemistry International, 23, 173-185.
[17] Pak, M.A., Haas, H.L., Decking, U.K. and Schrader, J. (1994) Inhibition of adenosine Kinase Increases Endogenous Adenosine and Depresses Neuronal Activity in Hippocampal Slices. Neuropharmacology, 33, 1049-1053.
[18] Lloyd, H.G. and Fredholm, B.B. (1995) Involvement of Adenosine Deaminase and Adenosine Kinase in Regulating Extracellular Adenosine Concentration in Rat Hippocampal Slices. Neurochemistry International, 26, 387-395.
[19] Fastbom, J., Pazos, A. and Palacios, J.M. (1987) The Distribution of Adenosine A1 Receptors and 5'-Nucleotidase in the Brain of Some Commonly Used Experimental Animals. Neuroscience, 22, 813-826.
[20] Latini, S. and Pedata, F. (2001) Adenosine in the Central Nervous System: Release Mechanisms and Extracellular Concentrations. Journal of Neurochemistry, 79, 463-484.
[21] Zimmermann, H. (1996) Biochemistry, Localization and Functional Roles of Ecto-Nucleotidases in the Nervous System. Progress in Neurobiology, 49, 589-618.
[22] Dunwiddie, T.V., Diao, L. and Proctor, W.R. (1997) Adenine Nucleotides Undergo Rapid, Quantitative Conversion to Adenosine in the Extracellular Space in Rat Hippocampus. Journal of Neuroscience, 17, 7673-7682.
[23] Geiger, J.D. and Fyda, D.M. (1991) Adenosine Transport in Nervous Tissues. In: Stone, T.W., Ed., Adenosine in the Nervous System, Academic Press, London, 1-23.
[24] Bender, A.S., Wu, P.H. and Phillis, J.W. (1981) The Rapid Uptake and Release of [3H] Adenosine by Rat Cerebral Cortical Synaptosomes. Journal of Neurochemistry, 36, 651-660.
[25] Brundege, J.M. and Dunweddie, T.V. (1997) Role of Adenosine as a Modulator of Synaptic Activity in the Central Nervous System. Advances in Pharmacology, 39, 353-391.
[26] Brundege, J.M. and Dunweddie, T.V. (1996) Modulation of the Excitatory Synaptic Transmission by Adenosine Relased from Single Hippocampal Pyramidal Neurons. Journal of Neuroscience, 16, 5603-5612.
[27] Sperlagh, B. and Vizi, E.S. (2011) The Role of Extracellular Adenosine in Chemical Neurotransmission in the Hippocampus and Basal Ganglia: Pharmacological and Clinical Aspects. Current Topics in Medicinal Chemistry, 11, 1034-1046.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.