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      Release of Adenosine and ATP During Ischemia and Epilepsy

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      Current Neuropharmacology
      Bentham Science Publishers Ltd.

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          Abstract

          Eighty years ago Drury & Szent-Györgyi described the actions of adenosine, AMP (adenylic acid) and ATP (pyrophosphoric or diphosphoric ester of adenylic acid) on the mammalian cardiovascular system, skeletal muscle, intestinal and urinary systems. Since then considerable insight has been gleaned on the means by which these compounds act, not least of which in the distinction between the two broad classes of their respective receptors, with their many subtypes, and the ensuing diversity in cellular consequences their activation invokes. These myriad actions are of course predicated on the release of the purines into the extracellular milieu, but, surprisingly, there is still considerable ambiguity as to how this occurs in various physiological and pathophysiological conditions. In this review we summarise the release of ATP and adenosine during seizures and cerebral ischemia and discuss mechanisms by which the purines adenosine and ATP may be released from cells in the CNS under these conditions.

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          Most cited references221

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          Astrocytic purinergic signaling coordinates synaptic networks.

          To investigate the role of astrocytes in regulating synaptic transmission, we generated inducible transgenic mice that express a dominant-negative SNARE domain selectively in astrocytes to block the release of transmitters from these glial cells. By releasing adenosine triphosphate, which accumulates as adenosine, astrocytes tonically suppressed synaptic transmission, thereby enhancing the dynamic range for long-term potentiation and mediated activity-dependent, heterosynaptic depression. These results indicate that astrocytes are intricately linked in the regulation of synaptic strength and plasticity and provide a pathway for synaptic cross-talk.
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            Adenosine receptors as therapeutic targets.

            Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer.
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              The role and regulation of adenosine in the central nervous system.

              Adenosine is a modulator that has a pervasive and generally inhibitory effect on neuronal activity. Tonic activation of adenosine receptors by adenosine that is normally present in the extracellular space in brain tissue leads to inhibitory effects that appear to be mediated by both adenosine A1 and A2A receptors. Relief from this tonic inhibition by receptor antagonists such as caffeine accounts for the excitatory actions of these agents. Characterization of the effects of adenosine receptor agonists and antagonists has led to numerous hypotheses concerning the role of this nucleoside. Previous work has established a role for adenosine in a diverse array of neural phenomena, which include regulation of sleep and the level of arousal, neuroprotection, regulation of seizure susceptibility, locomotor effects, analgesia, mediation of the effects of ethanol, and chronic drug use.
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                Author and article information

                Journal
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers Ltd.
                1570-159X
                1875-6190
                September 2009
                : 7
                : 3
                : 160-179
                Affiliations
                []Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK
                Author notes
                [* ]Address correspondence to this author at Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK; Tel: 02476 150591; Fax: 02476 523701; E-mail: b.g.frenguelli@ 123456warwick.ac.uk
                Article
                CN-7-160
                10.2174/157015909789152146
                2769001
                20190959
                def75d55-1ab4-40fe-9989-9236827a5bff
                ©2009 Bentham Science Publishers Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 February 2009
                : 15 April 2009
                : 1 May 2009
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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