HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thompson, S M Articles by Gähwiler, B H Search for Related Content PubMed PubMed Citation Articles by Thompson, S M Articles by Gähwiler, B H

Brain Research Institute, University of Zurich, Switzerland.

1. Intracellular microelectrode recordings were used to study the cellular location, the receptor pharmacology, and the mechanism of action of adenosine on pyramidal cells and presynaptic axonal endings in area CA3 of organotypic hippocampal slice cultures. 2. Adenosine (bath applied at 50 microM) caused a 10-15 mV hyperpolarization of CA3 cells, as well as a 75-100% decrease in the amplitude of excitatory and polysynaptic inhibitory postsynaptic potentials (EPSPs and IPSPs). Adenosine had no effect on the amplitude of monosynaptic IPSPs elicited in the presence of excitatory amino acid receptor antagonists, but did reduce the amplitude of isolated EPSPs, elicited after blocking GABAA receptors and reducing subsequent epileptic bursts with excitatory amino acid receptor antagonists. These data indicate that adenosine receptors are located on excitatory, but not inhibitory, presynaptic elements. 3. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, bath applied at 200 nM) blocked the pre- and postsynaptic actions of adenosine. DPCPX had no effect on the amplitude of control synaptic responses, suggesting that there is no tonic activation of adenosine receptors in hippocampal slice cultures under control conditions. The A1 receptor agonists R-N6-phenylisopropyladenosine (R-PIA) mimicked all pre- and postsynaptic actions of adenosine. 4. Pertussis toxin pretreatment (500 ng/ml for 48 h) prevented adenosine from activating postsynaptic K+ conductance, but not from inhibiting EPSPs. In contrast, stimulation of protein kinase C with phorbol ester (phorbol 12, 13-dibutyrate, 1 microM for 10 min) reduced the presynaptic, but not the postsynaptic, actions of adenosine. 5. Barium (bath applied at 1 mM) blocked the adenosine-activated K+ conductance, but not the inhibition of isolated EPSPs by adenosine. 6. Adenosine at 0.03-1 microM reduced the frequency of, or blocked, spontaneous epileptiform bursting produced by bicuculline. DPCPX (200 nM) increased the rate of spontaneous bursting, consistent with a tonic activation of adenosine receptors during hyperactivity, and led to the development of prolonged ictal-like bursts, suggesting that the endogenous release of adenosine may contribute to the termination of epileptic bursts. 7. We conclude that adenosine acts at pre- and postsynaptic receptors which are pharmacologically indistinguishable. Postsynaptically, adenosine increases a barium-sensitive K+ conductance via a pertussis toxin-sensitive GTP-binding protein. The presynaptic action of adenosine must, however, be mediated by some other mechanism.

This article has been cited by other articles:

				S. S. Mathew, L. Pozzo-Miller, and J. J. Hablitz Kainate Modulates Presynaptic GABA Release from Two Vesicle Pools J. Neurosci., January 16, 2008; 28(3): 725 - 731. [Abstract] [Full Text] [PDF]

				A. E. Fink, J. Sarinana, E. E. Gray, and T. J. O'Dell Activity-Dependent Depression of Local Excitatory Connections in the CA1 Region of Mouse Hippocampus J Neurophysiol, June 1, 2007; 97(6): 3926 - 3936. [Abstract] [Full Text] [PDF]

				B. Lasztoczi and J. Kardos Cyclothiazide Prolongs Low [Mg2+]-Induced Seizure-Like Events J Neurophysiol, December 1, 2006; 96(6): 3538 - 3544. [Abstract] [Full Text] [PDF]

				K. Yang, T. Fujita, and E. Kumamoto Adenosine Inhibits GABAergic and Glycinergic Transmission in Adult Rat Substantia Gelatinosa Neurons J Neurophysiol, November 1, 2004; 92(5): 2867 - 2877. [Abstract] [Full Text] [PDF]

				D. H. Brager, P. W. Luther, F. Erdelyi, G. Szabo, and B. E. Alger Regulation of Exocytosis from Single Visualized GABAergic Boutons in Hippocampal Slices J. Neurosci., November 19, 2003; 23(33): 10475 - 10486. [Abstract] [Full Text] [PDF]

				H.-J. Jeong, I.-S. Jang, J. Nabekura, and N. Akaike Adenosine A1 Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in Immature Rat Hippocampal CA1 Neurons J Neurophysiol, March 1, 2003; 89(3): 1214 - 1222. [Abstract] [Full Text] [PDF]

				D. H. Brager and S. M. Thompson Activity-Dependent Release of Adenosine Contributes to Short-Term Depression at CA3-CA1 Synapses in Rat Hippocampus J Neurophysiol, January 1, 2003; 89(1): 22 - 26. [Abstract] [Full Text] [PDF]

				A. J. Straiker, C. R. Borden, and J. M. Sullivan G-Protein alpha Subunit Isoforms Couple Differentially to Receptors that Mediate Presynaptic Inhibition at Rat Hippocampal Synapses J. Neurosci., April 1, 2002; 22(7): 2460 - 2468. [Abstract] [Full Text] [PDF]

				M. Kouznetsova, B. Kelley, M. Shen, and S. A. Thayer Desensitization of Cannabinoid-Mediated Presynaptic Inhibition of Neurotransmission Between Rat Hippocampal Neurons in Culture Mol. Pharmacol., March 1, 2002; 61(3): 477 - 485. [Abstract] [Full Text] [PDF]

				J. P. Wetherington and N. A. Lambert Differential Desensitization of Responses Mediated by Presynaptic and Postsynaptic A1 Adenosine Receptors J. Neurosci., February 15, 2002; 22(4): 1248 - 1255. [Abstract] [Full Text] [PDF]

				D. Centonze, E. Saulle, A. Pisani, G. Bernardi, and P. Calabresi Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia Brain, September 1, 2001; 124(9): 1855 - 1865. [Abstract] [Full Text] [PDF]

				S. A. Deuchars, R. E. Brooke, and J. Deuchars Adenosine A1 Receptors Reduce Release from Excitatory But Not Inhibitory Synaptic Inputs onto Lateral Horn Neurons J. Neurosci., August 15, 2001; 21(16): 6308 - 6320. [Abstract] [Full Text] [PDF]

				Y. Tohdoh, E. Narimatsu, M. Kawamata, and A. Namiki The Involvement of Adenosine Neuromodulation in Pentobarbital-Induced Field Excitatory Postsynaptic Potentials Depression in Rat Hippocampal Slices Anesth. Analg., December 1, 2000; 91(6): 1537 - 1541. [Abstract] [Full Text] [PDF]

				J. M. Bissonnette Mechanisms regulating hypoxic respiratory depression during fetal and postnatal life Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1391 - R1400. [Abstract] [Full Text] [PDF]

				J. C. Rekling, G. D. Funk, D. A. Bayliss, X.-W. Dong, and J. L. Feldman Synaptic Control of Motoneuronal Excitability Physiol Rev, April 1, 2000; 80(2): 767 - 852. [Abstract] [Full Text] [PDF]

				J. B. Wiesner, B. G. Ugarkar, A. J. Castellino, J. Barankiewicz, D. P. Dumas, H. E. Gruber, A. C. Foster, and M. D. Erion Adenosine Kinase Inhibitors as a Novel Approach to Anticonvulsant Therapy J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1669 - 1677. [Abstract] [Full Text]

				W. P. Luk, Y. Zhang, T. D. White, F. A. Lue, C. Wu, C.-G. Jiang, L. Zhang, and H. Moldofsky Adenosine: a Mediator of Interleukin-1beta -Induced Hippocampal Synaptic Inhibition J. Neurosci., June 1, 1999; 19(11): 4238 - 4244. [Abstract] [Full Text] [PDF]

				B. B. Fredholm, K. Battig, J. Holmen, A. Nehlig, and E. E. Zvartau Actions of Caffeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use Pharmacol. Rev., March 1, 1999; 51(1): 83 - 133. [Abstract] [Full Text] [PDF]

				K. E. Vogt and R. A. Nicoll Glutamate and gamma -aminobutyric acid mediate a heterosynaptic depression at mossy fiber synapses in the hippocampus PNAS, February 2, 1999; 96(3): 1118 - 1122. [Abstract] [Full Text] [PDF]

				D. L. Sodickson and B. P. Bean Neurotransmitter Activation of Inwardly Rectifying Potassium Current in Dissociated Hippocampal CA3 Neurons: Interactions among Multiple Receptors J. Neurosci., October 15, 1998; 18(20): 8153 - 8162. [Abstract] [Full Text] [PDF]

				V. Tancredi, M. D'Antuono, A. Nehlig, and M. Avoli Modulation of Epileptiform Activity by Adenosine A1 Receptor-Mediated Mechanisms in the Juvenile Rat Hippocampus J. Pharmacol. Exp. Ther., September 1, 1998; 286(3): 1412 - 1419. [Abstract] [Full Text]

				M. Shen and S. A. Thayer Cannabinoid Receptor Agonists Protect Cultured Rat Hippocampal Neurons from Excitotoxicity Mol. Pharmacol., September 1, 1998; 54(3): 459 - 462. [Abstract] [Full Text]

				T. V. Dunwiddie, L. Diao, and W. R. Proctor Adenine Nucleotides Undergo Rapid, Quantitative Conversion to Adenosine in the Extracellular Space in Rat Hippocampus J. Neurosci., October 15, 1997; 17(20): 7673 - 7682. [Abstract] [Full Text] [PDF]

				Y. Yuan and W. D. Atchison Action of Methylmercury on GABAA Receptor-Mediated Inhibitory Synaptic Transmission Is Primarily Responsible for Its Early Stimulatory Effects on Hippocampal CA1 Excitatory Synaptic Transmission J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 64 - 73. [Abstract] [Full Text]

				P. Calabresi, D. Centonze, A. Pisani, and G. Bernardi Endogenous Adenosine Mediates the Presynaptic Inhibition Induced by Aglycemia at Corticostriatal Synapses J. Neurosci., June 15, 1997; 17(12): 4509 - 4516. [Abstract] [Full Text] [PDF]

				G. Chen and A. N. van den Pol Adenosine Modulation of Calcium Currents and Presynaptic Inhibition of GABA Release in Suprachiasmatic and Arcuate Nucleus Neurons J Neurophysiol, June 1, 1997; 77(6): 3035 - 3047. [Abstract] [Full Text] [PDF]

				T. V. Dunwiddie, L. Diao, H. O. Kim, J.-L. Jiang, and K. A. Jacobson Activation of Hippocampal Adenosine A3 Receptors Produces a Desensitization of A1 Receptor-Mediated Responses in Rat Hippocampus J. Neurosci., January 15, 1997; 17(2): 607 - 614. [Abstract] [Full Text] [PDF]

				J. Doherty and R. Dingledine Regulation of Excitatory Input to Inhibitory Interneurons of the Dentate Gyrus During Hypoxia J Neurophysiol, January 1, 1997; 77(1): 393 - 404. [Abstract] [Full Text] [PDF]