Summary
Slices of the head of the rabbit caudate nucleus were preincubated with 10−7 M 3H-dopamine and then superfused, and the effect of unlabeled dopamine on the outflow of tritium was investigated. In most experiments, nomifensine was added throughout superfusion in order to block uptake of the unlabeled amine. Nomifensine was a potent inhibitor of the uptake of 3H-dopamine into rabbit caudate synaptosomes, with an IC50 of 5·10−8 M at a 3H-dopamine concentration of 4·10−8 M.
In the absence of nomifensine, unlabeled dopamine (10−7 M and higher concentrations) accelerated the basal outflow of tritium from preincubated slices. 10−5 M nomifensine strongly counteracted the acceleration. In the presence of nomifensine, unlabeled dopamine (10−7 to 10−6 M) caused a concentrationdependent decrease of the overflow of tritium evoked by electrical stimulation at 0.1 Hz. Chlorpromazine and haloperidol (in the presence of nomifensine) increased the stimulation evoked overflow and antagonized the inhibitory effect of dopamine.
It is concluded that extracellular dopamine shares with other dopaminergic agonists the ability to inhibit action potential-evoked release of intraneuronal dopamine. The inhibition is mediated by specific receptors. The results support the hypothesis that previously released dopamine, by an action on these receptors, can inhibit further release of dopamine.
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References
Farnebo, L. O., Hamberger, B.: Drug-induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta Physiol. Scand. 84, Suppl. 371, 35–44 (1971)
Graefe, K. H.: Methodology of catecholamine transport studies: definition of terms. In: The mechanism of neuronal and extraneuronal transport of catecholamines (D. M. Paton, ed.), pp. 7–35. New York: Raven Press 1976
Horn, A. S.: Characteristics of transport in dopaminergic neurons. In: The mechanism of neuronal and extraneuronal transport of catecholamines (D. M. Paton, ed.), pp. 195–214. New York: Raven Press 1976
Hunt, P., Kannengiesser, M. H., Raynaud, J. P.: Nomifensine: a new potent inhibitor of dopamine uptake into synaptosomes from rat brain corpus striatum. J. Pharm. Pharmacol. 26, 370–371 (1974)
Hyttel, J.: Ihhibition of [3H] dopamine accumulation in trat striatal synaptosomes by psychotropic drugs. Biochem. Pharmacol. 27, 1063–1068 (1978)
Lineweaver, H., Burk, D.: The determination of enzyme dissociation constants. J. Am. Chem. Soc. 56, 658–666 (1934)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275 (1951)
Perkins, N. A., Westfall, T. C.: Drug-induced alterations in the fieldstimulated release of 3H-dopamine from slices of rat striatum and median eminence. Neurosci. Abstr. 6, 499 (1976)
Plotsky, P. M., Wightman, R. M., Chey, W., Adams, R. N.: Liquid chromatographic analysis of endogenous catecholamine released from brain slices. Science 197, 904–906 (1977)
Raiteri, M., Cervoni, A. M., del Carmine, R., Levi, G.: Lack of presynaptic autoreceptors controlling dopamine release in striatal synaptosomes. In: Presynaptic receptors (S. Z. Langer, K. Starke, M. L. Dubocovich, eds.) New York: Pergamon Press (in press, 1979)
Seeman, P., Lee, T.: Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217–1219 (1975)
Starke, K.: Presynaptic modulation of catecholamine release in the central nervous system: some open questions. In: Presynaptic receptors (S. Z. Langer, K. Starke, M. L. Dubocovich, eds.). New York: Pergamon Press (in press, 1979)
Starke, K., Montel, H.: Alpha-receptor-mediated modulation of transmitter release from central noradrenergic neurones. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 53–60 (1973)
Starke, K., Montel, H., Wagner, J.: Effect of phentolamine on noradrenaline uptake and release. Naunyn-Schmiedeberg's Arch. Pharmacol. 271, 181–192 (1971)
Starke, K., Reimann, W., Zumstein, A., Hertting, G.: Effect of dopamine receptor agonists and antagonists on release of dopamine in the rabbit caudate nucleus in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 27–36 (1978)
Tuomisto, J.: Nomifensine and its derivatives as possible tools for studying amine uptake. Eur. J. Pharmacol. 42, 101–106 (1977)
Westfall, T. C., Besson, M. J., Giorguieff, M. F., Glowinski, J.: The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 279–287 (1976)
Westfall, T. C., Perkins, N. A., Paul, C.: Role of presynaptic receptors in the synthesis and release of dopamine in the mammalian central nervous system. In: Presynaptic receptors (S. Z. Langer, K. Starke, M. L. Dubocovich, eds.). New York: Pergamon Press (in press, 1979)
Whittaker, V. P., Barker, L. A.: The subcellular fractionation of brain tissue with special reference to the preparation of synaptosomes and their component organelles. In: Methods of neurochemistry (R. Fried, ed.), Vol. 2, pp. 1–52. New York: Marcel Dekker 1972
Wilkinson, G. N.: Statistical estimations in enzyme kinetics. Biochem. J. 80, 324–332 (1961)
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Reimann, W., Zumstein, A., Jackisch, R. et al. Effect of extracellular dopamine on the release of dopamine in the rabbit caudate nucleus: Evidence for a dopaminergic feedback inhibition. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 53–60 (1979). https://doi.org/10.1007/BF00515593
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DOI: https://doi.org/10.1007/BF00515593