Summary
We have found that ethanol-induced increases in extracellular adenosine activate adenosine receptors which, in turn, mediate many of the acute and chronic effects of ethanol in the nervous system. Several laboratories have demonstrated the importance of adenosine in mediating the acute and chronic effects of ethanol at multiple levels of investigation in the nervous system. These include genetic selection for ethanol sensitivity in mice, behavioral responses to ethanol in naive and tolerant animals, neurophysiologic responses in hippocampal slices, and at the level of cAMP signal transduction and gene expression in cultured neural cells. In this review we present results from our laboratory which document the role of adenosine in mediating ethanol-induced changes in neural function at a cellular and molecular level. A schematic summary of our findings is:
EtOH → ↓ Ado uptake → ↑ Extracellular Ado → Activation of Adenosine A2 receptor → ↑ cAMP → ↑ t PKA →→→ Heterologous Desensitization (↓ cAMP) →→→ insensitivity of adenosine uptake to EtOH
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References
Bruns, R.F. (1990) Adenosine receptors: roles and pharmacology. Ann. NY Acad. Sci.603: 211–226.
Cullen, N. and Carlen, P.L. (1992) Electrophysiological actions of acetate, a metabolite of ethanol, on hippocampal dentate granule neurons: interactions with adenosine. Brain Res. 588: 49–57.
Dar, M.S. (1989) Central nervous system effects and behavioral interactions with ethanol of centrally administered dilazep and its metabolites in mice. Eur. J. Pharmacol.164: 303–313.
Dar, M.S. (1990a) Central adenosinergic system involvement in ethanol-induced motor in coordination in mice. J. Pharmacol. Exp. Ther.255: 1202–1209.
Dar, M.S. (1990b) Functional correlation between subclasses of brain adenosine receptor affinities and ethanol-induced motor incoordination in mice. Pharmacol. Biochem. & Behay.37: 747–753.
Dar, M.S. and Clark, M. (1992) Tolerance to adenosine’s accentuation of ethanol-induced motor incoordination in ethanol-tolerant mice. Alcohol. Clin. Exp. Res. 16: 1138–1146.
Dar, M.S., Hardee, M. and Ganey, T. (1989) Brain adenosine modulation of behavioral interactions between ethanol and carbamazepine in mice. Alcohol6: 297–301.
Dar, M.S., Jones, M., Close, G., Mustafa, S.J. and Wooles, W.R. (1987) Behavioral interactions of ethanol and methylxanthines. Psychopharmacology91: 1–4.
Diamond, I., Nagy, L., Mochly-Rosen, D. and Gordon, A. (1991) The role of adenosine and adenosine transport in ethanol-induced cellular tolerance and dependence. Ann. NY Acad. Sci.625: 473–487.
Diamond, I., Wrubel, B., Estrin, E. and Gordon, A.S. (1987) Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients. Proc. Natl. Acad. Sci. USA84: 1413–1416.
Dunwiddie, T.V. (1985) The physiological role of adenosine in the central nervous system. Academic Press, Inc., Denver, pp. 63–139.
Ferre, S., Fuxe, K., von Euler, G., Johansson, B. and Fredholm, B.B. (1992) Adenosine-dopamine interactions in the brain. Neuroscience51: 501–512.
Ferre, S., von Euler, G., Johansson, B., Fredholm, B.B. and Fuxe, K. (1991) Stimulation of high-affinity adenosine A, receptors decreases the affinity of dopamine D, receptors in rat striatal membranes. Proc. Natl. Acad. Sci. USA88: 7238–7241.
Gordon, A.S., Collier, K. and Diamond, I. (1986) Ethanol regulation of adenosine receptor-dependent cAMP levels in a clonal neural cell line: An in vitromodel of cellular tolerance to ethanol. Proc. Natl. Acad. Sci. USA83: 2105–2108.
James, S. and Richardson, P.J. (1993) Production of adenosine from extracellular ATP at the striatal cholinergic synapse. J. Neurochem.60: 219–227.
Karunanithi, S., Lavidis, N.A. and Bennett, M.R. (1992) The effect of adenosine on spontaneous and evoked quantal secretion from different release sites of amphibian motor-nerve terminals. Neurosci. Lett.147: 49–52.
Krauss, S.W., Ghirnikar, R.B., Diamond, I. and Gordon, A.S. (1993) Inhibition of adenosine uptake by ethanol is specific for one class of nucleoside transporters. Mol. Pharmacol., 44: 1021–1026.
Lupica, C.R., Proctor, W.R. and Dunwiddie, T.V. (1992) Presynaptic inhibition of excitatory synaptic transmission by adenosine in rat hippocampus: Analysis of unitary EPSP variance measured by whole-cell recording. J. Neurosci.12: 3753–3764.
Mochly-Rosen, D., Chang, F.-U., Cheever, L., Kim, M., Diamond, I. and Gordon, A.S. (1988) Chronic ethanol causes heterologous desensitization by reducing a, mRNA. Nature333: 848–850.
Nagy, L.E., Diamond, I., Casso, D.J., Franklin, C. and Gordon, A.S. (1990) Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter. J. Biol. Chem.265: 1946–1951.
Nagy, L.E., Diamond, I., Collier, K., Lopez, L., Ullman, B. and Gordon, A.S. (1989) Adenosine is required for ethanol-induced heterologous desensitization. Mol. Pharmacol.36: 744–748.
Nagy, L.E., Diamond, I. and Gordon, A.S. (1991) cAMP-dependent protein kinase regulates inhibition of adenosine transport by ethanol. Mol. Pharmacol. 40: 812–817.
Olah, M.E. and Stiles, G.L. (1992) Adenosine receptors. Ann. Rev. Physiol.54: 211–225.
Phillis, J.W., O’Regan, M.H. and Walter, G.A. (1989) Effects of two nucleoside transport inhibitors, dipyridamole and soluflazine, on purine release from the rat cerebral cortex. Brain Res. 481: 309–316.
Phillis, J.W. and Wu, P.H. (1981) The role of adenosine and its nucleotides in central synaptic transmission. Prog. Neurobiol.16: 187–239.
Pitchford, S., Day, J.W., Gordon, A. and Mochly-Rosen, D. (1992) Nicotinic acetylcholine receptor desensitization is regulated by activation-induced extracellular adenosine accumulation. J. Neurosci.12: 4540–4544.
Prince, D.A. and Stevens, C.F. (1992) Adenosine decreases neurotransmitter release at central synapses. Proc. Nad. Acad. Sci. USA89: 8586–8690.
Proctor, W.R., Baker, R.C. and Dunwiddie, T.V. (1985) Differential CNS sensitivity to PIA and theophylline in long-sleep and short-sleep mice. Alcohol2: 287–291.
Proctor, W.R. and Dunwiddie, T.V. (1984) Behavioral sensitivity to purinergic drugs parallels ethanol sensitivity in selectively bred mice. Science224: 519–521.
Rubio, R., Bencherif, M. and Berne, R.M. (1989) Inositol phospholipid metabolism during the following synaptic activation: role of adenosine. J. Neurochem.52: 797–806.
Rudolphi, K.A., Schubert, P., Parkinson, F.E. and Fredholm, B.B. (1992) Neuroprotective role of adenosine in cerebral ischaemia. TIPS13: 439–445.
Scholz, K.P. and Miller, R.J. (1992) Inhibition of quantal transmitter release in the absence of calcium influx by a G protein-linked adenosine receptor at hippocampal synapses. Neuron8: 1139–1150.
Stiles, G.L. (1990) Adenosine receptors and beyond: molecular mechanisms of physiological regulation. Clin. Res.88: 10–18.
Stiles, G.L. (1992) Adenosine receptors. J. Biol. Chem.267: 6451–6454.
Yoon, K.-W. and Rothman, S.M. (1991) Adenosine inhibits excitatory but not inhibitory synaptic transmission in the hippocampus. J. Neurosci.11: 1375–1380.
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© 1994 Birkhäuser Verlag Basel/Switzerland
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Diamond, I., Gordon, A.S. (1994). The role of adenosine in mediating cellular and molecular responses to ethanol. In: Jansson, B., Jörnvall, H., Rydberg, U., Terenius, L., Vallee, B.L. (eds) Toward a Molecular Basis of Alcohol Use and Abuse. Experientia, vol 71. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7330-7_18
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DOI: https://doi.org/10.1007/978-3-0348-7330-7_18
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