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Biochemical Pharmacology of Dopamine Receptors

  • M. Memo
  • E. Carboni
  • H. Uzumaki
  • S. Govoni
  • M. O. Carruba
  • M. Trabucchi
  • P. F. Spano
Part of the NATO ASI Series book series (NSSA, volume 72)

Abstract

Over the last few years, new biochemical methodologies have provided direct approaches to extensively investigate central dopaminergic receptors. It has been found that an adenylate cyclase preferentially stimulated by dopamine (DA) is present in several brain dopaminergic areas (16, 20, 35, 37). This finding first allowed a direct pharmacological characterization of compounds with agonist or antagonist properties at the DA receptor level and suggested that physiological responses following interaction between DA and its own receptor are mediated by activation of adenylate cyclase. However, the inhibitory potency of various antipsychotic drugs does not fully correlate with their behavioral and clinical efficacy (33), Moreover, we found that sulpiride and other substituted benzamides, which behave as strong DA antagonists in various animal tests and in clinical applications, fail to inhibit, in contrast to classical neuroleptics, the formation of cyclic AMP elicited by DA or apomorphine both in vitro and in vivo (37, 39, 48). In addition, we observed that some ergot derivatives, endowed with strong DA-mimetic properties in animals and in man, do not stimulate DA-sensitive adenylate cyclase activity in brain homogenates (37, 50). However, we and others have shown that substituted benzamides and dopaminergic ergot derivatives are capable of interacting specifically with central and peripheral DA receptors (15, 37, 39).

Keywords

Dopamine Receptor Adenylate Cyclase Vasoactive Intestinal Peptide Adenylate Cyclase Activity Ergot Alkaloid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Brown, J.N., and Makman, M.H., Stimulation by dopamine of adenylate cyclase in retinal homogenates and of adenosine 3’,5’-cyclic AMP formation in intact retina, Proc. Natl. Acad. Sci. USA, 69: 539–543, 1972.Google Scholar
  2. 2.
    Carboni, E., Memo, M., Trabucchi, M., and Spano, P.F., Temperature-dependency of 3H(-)sulpiride binding in various areas of rat brain (submitted for publication).Google Scholar
  3. 3.
    Carruba, M.O., Ricciardi, S., Müller, E.E., and Mantegazza, P., Anorectic effect of lisuride and other ergot derivatives in the rat, Eur. J. Pharmacol, 64: 133–141, 1980.Google Scholar
  4. 4.
    Clement-Cormier, Y.C., and Robinson, G.A., Adenylate cyclase from various dopaminergic areas of the brain and the action of antipsychotic drugs, Biochem. Pharmacol, 26: 1719–1722, 1977.Google Scholar
  5. 5.
    Cote, T.E., Crewe, C.W., and Kebabian, J.W., Stimulation of a D2-dopamine receptor in the intermediate lobe of rat pituitary gland decreases the responsiveness of the ß-adrenoreceptor: biochemical mechanism, Endocrinology, 108: 420–426, 1981.Google Scholar
  6. 6.
    Creese, I., Usdin, T.B., and Snyder, S.H., Dopamine receptor binding regulated by guanine nucleotides, Mol. Pharmacol, 16: 69–76, 1979.Google Scholar
  7. 7.
    Cuatrecasas, P., Membrane receptors, Annu. Rev. Biochem, 43: 169–214, 1974.Google Scholar
  8. 8.
    Dale, H.H., On some physiological actions of ergot, J. Physiol (London), 34: 163–206, 1906.Google Scholar
  9. 9.
    Da Prada, M., Bonetti, E.P., and Keller, H.H., Induction of mounting behavior in female and male rats by lisuride, Neurosci. Lett, 6: 349–353, 1977.Google Scholar
  10. 10.
    De Camilli, P., Macconi, D., and Spada, A., Dopamine inhibits adenylate cyclase in human prolacting-secreting pituitary adenomas, Nature (London), 278: 252–254, 1979.Google Scholar
  11. 11.
    De Haen, C., The non-stoichiometric floating receptor model for hormone-sensitive adenylate cyclase, J. Theor. Biol, 58: 383–400, 1976.Google Scholar
  12. 12.
    Fujita, N., Saito, K., Yonehara, N., and Yoshida, H., Lisuride inhibits 3H-spiroperidol binding to membranes isolated from striatum, Neuropharmacol, 17: 1089–1091, 1978.Google Scholar
  13. 13.
    Fuxe, K., and Calne, D.B., (eds), Dopaminergic Ergot Derivatives and Motor Function, Pergamon Press, Oxford, 1979.Google Scholar
  14. 14.
    Goldstein, M., Calne, D.B., Lieberman, A., and Thorner, M.O., (eds.), Advances in Biochemical Psychopharmacology, Vol. 24, Raven Press, New York, 1980.Google Scholar
  15. 15.
    Goldstein, M., Lew, J.Y., Hata, F., and Lieberman, A., Binding interactions of ergot alkaloids with monoaminergic receptors in the brain, Gerontology, 24: 76–85, 1978.Google Scholar
  16. 16.
    Horn, A.S., Cuello, A.C., and Miller, R.J., Dopamine in the mesolimbic system of rat brain: endogeneous levels and the effect of drugs on the up-take mechanisms and stimulation of adenylate cyclase, J. Neurochem, 22: 265–270, 1974.Google Scholar
  17. 17.
    Horowski, R., Differences in the dopaminergic effects of the ergot derivatives bromocriptine, lisurdie, and d-LSD as compared with apomorphine Eur. J. Pharmacol, 51: 157–166, 1978.Google Scholar
  18. 18.
    Hyttel, J., Characterization of 3H-GABA receptor binding to rat brain synaptosomal membranes: effect of non-GABAergic compounds, Psychopharmacol, 65: 211–214, 1979.Google Scholar
  19. 19.
    Kebabian, J.W., and Greengard, P., Dopamine-sensitive adenylate cyclase: possible role in synaptic transmission, Science, 174: 1346–1349, 1971.Google Scholar
  20. 20.
    Kebabian, J.W., Petzold, G.L., and Greengard, P., Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain and its similarity to the “dopamine receptor,” Proc. Natl. Acad. Sci. USA, 69: 2145–2149, 1972.Google Scholar
  21. 21.
    Kebabian J.W., Caine, D.B., and Kebabian, P.R., Lergotrile mesylate: an in vivo dopamine agonist which blocks dopamine receptors in vitro, Comm. Psychopharmacol, 1: 311–318, 1977.Google Scholar
  22. 22.
    Kebabian, J.W., and Calne, D.B., Multiple receptors for dopamine, Nature, 277: 93–96, 1979.CrossRefGoogle Scholar
  23. 23.
    Keller, H.H., and Da Prada, M., Central dopamine agonistic activity and microsomal biotransformation of lisuride, lergotrile and bromocriptine, Life Sci, 24: 1211–1222, 1979.Google Scholar
  24. 24.
    Liuzzi, A., Chiodini, P.G., Opizzi, G., Botalla, L., Verde, G., De Stefano, L., Colussi, G., Graf, K.J., and Horowski, R., Lisuride hydrogen maleate: evidence for a long-lasting dopaminergic activity in humans, J. Clin. Endocrinol. Metab, 46: 196–202, 1978.Google Scholar
  25. 25.
    Memo, M., Lovenberg, W., and Hanbauer, 1., Agonist-induced sub-sensitivity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum, Proc. Natl. Acad. Sci. USA, 79: 4456–4460, 1982.Google Scholar
  26. 26.
    Memo, M., Govoni, S., Carboni, E., Trabucchi, M., and Spano, P.F., Characterization of stereospecific binding of 3H-(-)sulpiride, a selective antagonist at dopamine-D2 receptors, in rat CNS, Pharmacol. Res. Comm, 15: 191–199, 1983.Google Scholar
  27. 27.
    Memo, M. Carboni, E., and Spano, P.F., Dopamine inhibits neurotensin-induced prolactin release by interacting with calcium channel rather than adenylate cyclase systems, Soc. Neurosci. Abstr, 1983, in press.Google Scholar
  28. 28.
    Nickerson, M., The pharmacology of adrenergic blockade, Pharmacol. Rev, 1: 27–101, 1969.Google Scholar
  29. 29.
    Onali, F.L., Schwartz, J.P., and Costa, E., Dopaminergic modulation of adenylate cyclase stimulation by vasoactive intestinal peptide in anterior pituitary, Proc. Natl. Acad. Sci USA, 78: 6531–6534, 1981.Google Scholar
  30. 30.
    Pieri, L., Keller, H.H., Burkard, W., and Da Prada, M., Effects of lisuride and LSD on cerebral monoamine systems and hallucinosis, Nature, 272: 278–280, 1978.Google Scholar
  31. 31.
    Pieri, M., Schaffner, R., Pieri, L., Da Prada, M., and Haefely, W., Turning in MFB-lesioned rats and antagonism on neuroleptic-induced catalepsy after lisuride and LSD., Life Sci, 22: 1615–1622, 1978.Google Scholar
  32. 32.
    Saiani, L., Trabucchi, M., Tonon, G.C., and Spano, P.F., Bromocriptine and lisuride stimulate the accumulation of cyclic AMP in intact slices but not in homogenates of rat neostriatum., Neurosci. Lett, 14: 31–36, 1979.Google Scholar
  33. 33.
    Seeman, P., Lee, T., Chau-Wong, M., and Wong, K., Antipsychotic drugs doses and neuroleptic/dopamine receptors, Nature (London), 261: 717–719, 1976.CrossRefGoogle Scholar
  34. 34.
    Spano, P.F., Di Chiara, G., Tonon, G.C., and Trabucchi, M., A dopamine stimulated adenylate cyclase in rat substantia nigra., J. Neurochem, 27: 1565–1568, 1976.Google Scholar
  35. 35.
    Spano, P.F., Trabucchi, M., and Di Chiara, G., Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum, Science, 196: 1343–1345, 1977.Google Scholar
  36. 36.
    Spano, P.F., and Trabucchi, M., (eds.), Ergot Alkaloids, Pharmacology, Vol. 16, Suppl., 1, Karger, Basel, 1978.Google Scholar
  37. 37.
    Spano, P.F., Govoni, S., and Trabucchi, M., Studies on Pharmacological properties of dopamine receptor in various areas of the central nervous system, In: Advances in Biochemical Psychopharmacology, Raven Press, New York, 19: 155–165, 1978.Google Scholar
  38. 38.
    Spano, P.F., Frattola, L., Govoni, S., Tonon, G.C., and Trabucchi, M., Dopaminergic ergot derivatives: selective agonists of a new class of dopamine receptors. In: Dopaminergic Ergot Derivatives and Motor Function, Fuxe, K., and Calne, D.B., (eds.), pp. 159–171, Pergamon Press, Oxford, 1979.Google Scholar
  39. 39.
    Spano, P.F., Stefanini, E., Trabucchi, M., and Fresia, P., Stereospecific interaction of sulpiride with striatal and nonstriatal dopamine receptors. In: Sulpiride and Other Benzamides, Spano, P.F., Trabucchi, M., Corsini, G.U., Cessa, G.L., (eds.), pp. -1–31, IBREF, Milan and Raven Press, New York, 1979.Google Scholar
  40. 40.
    Spano, P.F., Trabucchi, M., Corsini, G.U., and Cessa, G.L., (eds.), Sulpiride and Other Benzamides, IBREF, Milan; Raven Press, New York, 1979.Google Scholar
  41. 41.
    Spano, P.F., Saiani, L., Memo, M., and Trabucchi, M., Interaction of dopaminergic ergot derivatives with cyclic nucleotide system, In: Advances in Biochemical Pharmacology, Raven Press, New York, 23: 95–102, 1980.Google Scholar
  42. 42.
    Spano, P.F., Memo, M., Stefanini, E., Fresia, P., and Trabucchi, M., Detection of multiple receptors for dopamine, In: Receptor for Neurotransmitters and Peptide Hormones, Pepeu, G., Kuhar, M.J., and Enna, S.J., (eds.), pp. 243251, 1980, Raven Press, New York.Google Scholar
  43. 43.
    Spano, P.F., Govoni, S., Uzumaki, H., Bosi, A., Memo, M., Lucchi, L., Carruba, M., and Trabucchi, M., Stimulation of D2-dopamine receptors by dopaminergic ergot alkaloids: studies on the mechanism of action, Aging, 23: 165–177, 1983.Google Scholar
  44. 44.
    Spano, P.F., Carboni, E., Garau, L., Memo, M., Govoni, S., and Trabucchi, M., Sulpiride and other benzamides as specific antagonists at the D2 dopamine receptors, In: Receptors as Supramolecular Entities, Biggio, G., Costa, E., Cessa, G.L., and Spano, P.F., (eds.), Pergamon Press, 1983; in press.Google Scholar
  45. 45.
    Stefanini, E., Marchisio, A.M., Devoto, P., Vernaleone, F., Collu, R., and Spano, P.F., Sodium-dependent interaction of benzamides with dopamine receptors, Brain Res, 198: 229–233, 1980.Google Scholar
  46. 46.
    Stoof, J.C., and Kebabian, J.W., Opposing roles for D1 and D2 dopamine receptors in efflux of cyclic AMP from rat neostriatum, Nature, 294: 366–368, 1981.Google Scholar
  47. 47.
    Theodorou, A.E., Hall, M.D., Jenner, P., and Marsden, C.D., Cation regulation differentiates specific binding of 3H-sulpiride and 3H-spiroperone to rat striatal preparations, J. Pharm. Pharmacol, 32: 441–444, 1981.Google Scholar
  48. 48.
    Trabucchi, M., Longoni, R., Fresia, P., and Spano, P.F., Sulpiride a study of the effects on dopamine receptors in rat neostriatum and limbic forebrain, Life Sci, 17: 1551–1556, 1975.Google Scholar
  49. 49.
    Trabucchi, M., Govoni, S., Tonon, G.C., and Spano, P.F., Localization of dopamine receptors in the rat cerebral cortex, J. Pharm. Pharmacol, 28: 244–245, 1976.Google Scholar
  50. 50.
    Trabucchi, M., Spano, P.F., Tonon, G.C., and Frattola, L., Effect of bromocriptine on central dopaminergic receptors, Life Sci, 19: 225–232, 1976.Google Scholar
  51. 51.
    Uzumaki, H., Govoni, S., Memo, M., Carruba, M., Trabucchi, M., and Spano, P.F., Effects on GTP and sodium on rat striatal dopamine receptors labeled by 3H-lisuride, Brain Res, 248: 185–187, 1982.Google Scholar
  52. 52.
    Woodruff, G.N., Freedman, S.B., and Poat, J.A., Why does sulpiride not block the effect of dopamine on the dopamine-sensitive adenylate cyclase?, J. Pharm. Pharmacol, 32: 802–803, 1980.Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • M. Memo
    • 1
    • 2
  • E. Carboni
    • 1
    • 2
  • H. Uzumaki
    • 1
    • 2
  • S. Govoni
    • 1
    • 2
  • M. O. Carruba
    • 1
    • 2
  • M. Trabucchi
    • 1
    • 2
  • P. F. Spano
    • 1
    • 2
  1. 1.Department of Experimental Pharmacology and ToxicologyUniversity of CagliariItaly
  2. 2.Department of Pharmacology Schools of Pharmacy and MedicineUniversity of Milan ItalyItaly

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