Dopamine receptor mediated inhibition by pergolide of electrically-evoked 3H-dopamine release from striatal slices of cat and rat: Slight effect of ascorbate

  • John Lehmann
  • Sonia Arbilla
  • S. Z. Langer


The dopamine receptor agonist pergolide inhibited the calcium-dependent, electrically evoked overflow of tritium from slices of the striatum of cat or rat prelabelled with 3H-dopamine. This inhibition of tritium overflow by nanomolar concentrations of pergolide was antagonized by the benzamide neuroleptic S-sulpiride (0.1 μM). In millimolar concentrations, l- ascorbate had slight or no effects on this dopamine receptor mediated inhibition, in striatal slices of either the cat or the rat. Since these same concentrations of ascorbate have been reported to completely block the specific binding of 3H-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) and of 3H-apomorphine to presumed dopamine receptors, the present results suggest a dissociation between the characteristics of 3H-ADTN and 3H-apomorphine binding and the dopamine autoreceptor. Previous contradictory results concerning the existence of inhibitory dopamine receptors which modulate depolarization-evoked overflow of dopamine from the striatum of the rat are thus apparently not due to a species difference nor to the use of ascorbate, but rather to differences in experimental conditons.

Key words

Dopamine receptor Autoreceptor Neuroleptics Receptor binding Ascorbate 3H-dopamine release Caudate nucleus 


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  1. Arbilla S, Briley MS, Dubocovich ML, Langer SZ (1978) Neuroleptic binding and their effects on the spontaneous and potassium-evoked release of 3H-dopamine from the striatum and of 3H-noradrenaline from the cerebral cortex. Life Sci 23:1775–1780Google Scholar
  2. Arbilla S, Langer SZ, Lehmann J (1981) Dopamine autoreceptors inhibiting 3H-dopamine release in the caudate of the cat: evidence for a role of endogenously released dopamine. Br J Pharmacol (in press)Google Scholar
  3. Clement-Cormier Y, Abel M (1978) (3H)-2-Amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN): a potential specific dopamine receptor ligand. Res Commun Chem Phatol Pharmacol 22:15–25Google Scholar
  4. Cuatrecasas P, Hollenberg MD (1976) Membrane receptors and hormone action. Adv Protein Chem 30:251–451Google Scholar
  5. Demopoulos HB (1973) Control of free radicals in biologic systems. Fed Proc 32:1903–1908Google Scholar
  6. Dismukes K, Mulder AH (1977) Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum. Naunyn-Schmiedeberg's Arch Pharmacol 297:23–29Google Scholar
  7. Farnebo LO, Hamberger B (1971) Drug-induced changes in the release of 3H-dopamine from slices of rat corpus striatum. Acta Physiol Scand 84:[Suppl] 371:35–44Google Scholar
  8. Fuller RW, Clemens JA, Kornfeld EC, Snoddy HD, Smalstig EB, Bach NJ (1979) Effects of 8(8 β)-[(methylthio)methyl]-6-propylergoline on dopaminergic function and brain dopamine turnover in rats. Life Sci 24:375–382Google Scholar
  9. Goldstein M, Lieberman A, Lew JY, Asano T, Rosenfeld MR, Makman MH (1980) Interaction of pergolide with central dopaminergic receptors. Proc Natl Acad Sci USA 77:3725–3728Google Scholar
  10. Hoffman IS, Naylor RJ, Cubeddu LX (1980) Presynaptic effects of 2-amino tetralins on striatal dopaminergic neurons. J Pharmacol Exp Ther 215:486–493Google Scholar
  11. Kamal LA, Arbilla S, Langer SZ (1981) Presynaptic modulation of the release of dopamine from the rabbit caudate nucleus: Differences between electrical stimulation, amphetamine and tyramine. J Pharmacol Exp Ther 216:592–598Google Scholar
  12. Kayaalp SO, Neff NH (1980) Differentiation by ascorbic acid of dopaminergic agonist and antagonist binding sites in striatum. Life Sci 26:1837–1841Google Scholar
  13. Langer SZ, Arbilla S, Kamal L (1980) Autoregulation of noradrenaline and dopamine release through presynaptic receptors. In: Littauer UZ, Dudai Y, Silman I Teichberg VI, Vogel Z (eds) Neurotransmitters and their receptors. John Wiley and Sons Ltd., New York, pp. 7–21Google Scholar
  14. Lemberger L, Crabtree RE (1979) Pharmacologic effects in man of a potent, long-lasting dopamine receptor agonist. Science 205:1151–1153Google Scholar
  15. Leslie FM, Duncap CE, Cox BM (1980) Ascorbate decreases ligand binding to neurotransmitter receptors. J Neurochem 34:219–221Google Scholar
  16. Mcllwain H (1968) Membrane functioning in preparations from mammalian brain. Br Med Bull 24:174–178Google Scholar
  17. Plotsky PM, Wightman RM, Chey W, Adams RN (1977) Liquid chromatographic analysis of endogenous catecholamine released from brain slices. Science 197:904–906Google Scholar
  18. Seeman P, Chau-Wong M, Tedesco J, Wong K (1975) Brain receptor sites for antipsychotic drugs and dopamine: Direct binding assays. Proc Natl Acad Sci USA 72:4376–4380Google Scholar
  19. Seeman P, Lee T (1975) Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188:1217–1219Google Scholar
  20. Seeman P, Lee T, Chau-Wong M, Tedesco J, Wong K (1976) Dopamine receptors in human and calf brains, using (3H)apomorphine and an antipsychotic drug. Proc Nat Acad Sci USA 73:4354–4358Google Scholar
  21. Starke K, Reimann W, Zumstein A, Hertting G (1978) Effect of dopamine receptor agonists and antagonists on release of dopamine in the rabbit caudate nucleus in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 305:27–36Google Scholar
  22. Starke K (1979) Presynaptic modulation of catecholamine release in the central nervous system: some open questions. In: Langer SZ, Starke K, Dubocovich ML (eds) Presynaptic receptors, Pergamon, Oxford, pp 129–136Google Scholar
  23. Stoof JC, Horn AS, Mulder AH (1980) Simultaneous demonstration of the activation of presynaptic dopamine autoreceptors and postsynaptic dopamine receptors in vitro by N,N-dipropyl-5,6-ADTN. Brain Res 196:276–281Google Scholar
  24. Thal L, Creese I, Snyder SH (1978) 3H-Apomorphine interactions with dopamine receptors in calf brain. Eur J Pharmacol 49:295–299Google Scholar
  25. Thomas TN, Zemp JW (1977) Inhibition of dopamine sensitive adenylate cyclase from rat brain striatal homogenates by ascorbic acid. J Neurochem 28:663–665Google Scholar
  26. Westfall TC, Besson MJ, Giorguieff MF, Glowinski J (1976) The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of the rat striatum. Naunyn-Schmiedeberg's Arch Pharmacol 292:279–287Google Scholar
  27. Yen TT, Stamm NB, Clemens JA (1979) Pergolide: a potent dopaminergic antihypertensive. Life Sci 25:209–216Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • John Lehmann
    • 1
  • Sonia Arbilla
    • 1
  • S. Z. Langer
    • 1
  1. 1.Department of BiologyLaboratoires d'Etudes et de Recherches SynthélaboParisFrance

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