Summary
The release of both radioactive and endogenous purines was investigated in rat brain cortical, hippocampal and striatal slices at rest and following stimulation with electrical fields.
Purities were labelled by incubating the slices with 3H-adenine. The purine efflux at rest and that evoked by electrical stimulation (10 Hz, 5 min) was analyzed by HPLC with ultraviolet absorbance detection. Both radio-active and endogenous purines in the effluent consisted mainly of hypoxanthine, xanthine, inosine and adenosine. No qualitative differences in the composition of the released purines were found in the three areas investigated. Electrical stimulation evoked a net increase in both radioactive and endogenous purine release. However the increase in 3H-adenosine following electrical stimulation was twice as large as that of endogenous adenosine. The electrically evoked release of both radioactive and endogenous purines was greatest in hippocampal slices and progressively smaller in cortical and striatal slices. In the three areas the addition of 0.5 μM tetrodotoxin to the superfusing Krebs solution brought about a similar (83–100%) reduction in evoked 3H-purine and endogenous purine release. Superfusion of the slices with calcium-free Krebs solution containing 0.5 mM EGTA reduced evoked release of 3H-purines by 58–60% and that of endogenous purine components by 54–89%.
The results demonstrate similar characteristics for both radioactive and endogenous purine release but indicate that the most recently synthetized adenosine is the most readily available for release. The features of the electrically evoked purine release support a neuronal origin of adenosine and derivatives and are consistent with the hypothesis of discrete regional differences in adenosine neuromodulation.
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References
Abe M, Matsuda M (1983) On the existence of two GABA pools associated with newly synthetized GABA and with newly taken up GABA in nerve terminals. Neurochem Res 8:563–573
Ballarin M, Herrera Marschitz M, Casas M, Ungerstedt U (1987) Striatal adenosine levels measured “in vivo” by microdialysis in rats with unilateral dopamine denervation. Neurosci Lett 83:338–344
Bisserbe JC, Patel J, Marangos PJ (1985) Autoradiographic localization of adenosine uptake sites in rat brain using (3H)-nitrobenzylthiosionsine. J Neurosci 5:544–550
Braas KM, Newby AC, Wilson VS, Snyder SH (1986) Adenosine containing neurons in the brain localized by immunocytochemistry. J Neurosci 6:1952–1961
Daval JL, Barberis C (1981) Release of radiolabelled adenosine derivatives from superfused synaptosome beds. Evidence for the output of adenosine. Biochem Pharmacol 30:2559–2567
Deckert J, Bisserbe JC, Klein E, Marangos PJ (1988) Adenosine uptake sites in brain: regional distribution of putative subtypes in relationship to adenosine A1 receptors. J Neurosci 8:2338–2349
Dunwiddie TV (1985) The physiological roles of adenosine in the central nervous system. In: Smythies JR, Bradley RJ (eds) International Review of Neurobiology, Academic Press, London, pp 63–139
Fredholm BB, Sollevi A (1981) The release of adenosine and inosine from canine subcutaneus adipose tissue by nerve stimulation and noradrenaline. J Physiol (London) 313:351–367
Goodman RR, Snyder SH (1982) Autoradiographic localization of adenosine receptors in rat brain using 3H cyclohexiladenosine. J Neurosci 2:1230–1241
Herdon H, Strupish J, Nahorski SR (1985) Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition. Brain Res 348:309–320
Hollins C, Stone TW (1980) Characteristics of the release of adenosine from slices of rats cerebral cortex. J Physiol 303:73–82
Jackisch R, Strittmatter H, Kasakov L, Hertting G (1984) Endogenous adenosine as a modulator of hippocampal acetylcholine release. Naunyn-Schmiedeberg's Arch Pharmacol 327:319–325
Jonzon B, Fredholm BB (1985) Release of purines, noradrenaline, and GABA from rat hippocampal slices by field stimulation. J Neurochem 44:217–244
Kuroda Y, McIlwain H (1974) Uptake and release of 14C adenine derivatives at beds of mammalian cortical synaptosomes in a superfusion system. J Neurochem 22:691–699
MacDonald WF, White TD (1985) Nature of extrasynaptosomal accumulation of endogenous adenosine evoked by K+ and veratridine. J Neurochem 45:791–797
Marangos PJ, Patel J, Rosenberg RC, Martino AM (1982) 3H nitrobenzylthioinosine binding as a probe for the study of adenosine uptake sites in brain. J Neurochem 39:184–191
Narahashi T (1974) Chemicals as tools in the study of excitable membranes. Physiol Rev 54:813–888
Pedata F, Magnani M, Pepeu G (1988) Muscarinic modulation of purine release from electrically stimulated rat cortical slices. J Neurochem 50:1074–1079
Pedata F, Pazzagli M, Pepeu G (1989) Effects of caffeine on the release of purines from electrically stimulated cortical slices of control and caffeine treated rats. Neurosci Res Comm 5:163–169
Pedata F, Di Patre PL, Giovannini MG, Pazzagli M, PepeuG (1989) Cholinergic and noradrenergic denervation decrease labelled purine release from electrically stimulated rat cortical slices. Neuroscience 32:629–636
Perez MTR, Ehinger BE, Lindstrom K, Fredholm BB (1986) Release of endogenous and radioactive purines from the rabbit retina. Brain Res 398:106–112
Perez MTR, Arner K, Ehinger B (1988) Stimulation-evoked release of purines from the rabbit retina. Neurochem Int 13:307–318
Pons F, Bruns RF, Daly JW (1980) Depolarization-evoked accumulation of cyclic AMP in brain slices: the requisite intermediate adenosine is not derived from hydrolysis of released ATP. J Neurochem 34:1319–1323
Pull I, McIlwain H (1973) Output of 14C adenine nucleotides and their derivatives from central tissues. Biochem J 136:893–901
Schweinsberg PD, Loo TL (1980) Simultaneous analysis of ATP, ADP, AMP, and other purines in human erythrocytes by high-performance liquid chromatography. J Chromatogr 181:103–107
Snyder SH (1985) Adenosine as a neuromodulator. Ann Rev Neurosci 8:103–124
Stone TW (1981) Physiological roles for adenosine and adenosine 5′-triphosphate in the nervous system. Neuroscience 6:523–555
Van Wylen DGL, Park TS, Rubio R, Berne RB (1986) Increases in cerebral interstitial fluid adenosine concentration during hypoxia. Local potassium infusion and ischemia. J Cereb Blood Flow Metab 6:522–528
Williams M (1989) Adenosine the prototypic neuromodulator. Neurochem Int 14:249–264
Wojcik WJ, Neff NH (1983) Location of adenosine release and adenosine A2 receptors to rat striatal neurons. Life Sci 33:755–763
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Pedata, F., Pazzagli, M., Tilli, S. et al. Regional differences in the electrically stimulated release of endogenous and radioactive adenosine and purine derivatives from rat brain slices. Naunyn-Schmiedeberg's Arch Pharmacol 342, 447–453 (1990). https://doi.org/10.1007/BF00169463
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DOI: https://doi.org/10.1007/BF00169463