Biochemical and Behavioral Studies of D1 Dopamine Receptors Utilizing SCH 23390

  • Ellen J. Hess
  • Ian Creese
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 204)


Previous research has demonstrated the existence of two distinct dopamine receptor subtypes (Kebabian & Calne, 1979; Creese et al., 1983), possessing unique pharmacologic and biochemical properties. D1 dopamine receptors stimulate adenylate cyclase activity (Hyttel, 1978), while D2 dopamine receptors inhibit this enzyme (Stoof and Kebabian, 1981; Onali et al., 1984; Battaglia et al., 1985). However, both receptor subtypes co-exist in many tissues making the determination of their respective physiological and behavioral roles difficult. All neuroleptics, commonly used drugs in the treatment of schizophrenia, have been shown to be either mixed D1/D2 dopamine receptor antagonists or selective D2 dopamine receptor antagonists. Thus, D2 dopamine receptors have been implicated as the site mediating the antipsychotic and antidopaminergic activity of neuroleptics (Creese et al., 1976; Seeman et al., 1976). By inference, D2 dopamine receptors have been considered to mediate dopaminergic agonists’ behavioral effects as well (Seeman, 1981).


Dopamine Receptor Adenylate Cyclase Adenylate Cyclase Activity Dopamine Receptor Antagonist Dopamine Receptor Binding 
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  1. Andersen, P.H., Gronvald, F.C. and Jansen, J.A., 1985, A comparison between dopamine-stimulated adenylate cyclase and 3H-SCH 23390 binding in rat striatum, Life Sci., 37:1971–1983.PubMedCrossRefGoogle Scholar
  2. Arnt, J., 1985a, Behavioural stimulation is induced by separate dopamine D1 and D2 receptor sites in reserpine-pretreated by not in normal rats, Eur. J. Pharmacol., 113:79–88.PubMedCrossRefGoogle Scholar
  3. Arnt, J., 1985b, Hyperactivity induced by stimulation of separate dopamine D1 and D2 receptors in rats with bilateral 6-OHDA lesions, Life Sci., 37:717–723.PubMedCrossRefGoogle Scholar
  4. Arnt, J. and Hyttel, J., 1984, Differential inhibition by dopamine D1 and D2 antagonists of circling behaviour induced by dopamine agonists in rats with unilateral 6-hydroxydopamine lesions, Eur. J. Pharmacol., 102:349–354.PubMedCrossRefGoogle Scholar
  5. Arnt, J. and Hyttel, J., 1985, Differential involvement of dopamine D1 and D2 receptors in the circling behavior induced by apomorphine, SK&F 38393, pergolide and LY 171555 in 6-hydroxydopamine-lesioned rats, Psychopharmacol., 85:346–352.CrossRefGoogle Scholar
  6. Battaglia, G., Shannon, M. and Titeler, M., 1984, Guanyl nucleotide and divalent cation regulation of cortical S2 serotonin receptors, J. Neurochem., 43:1213–1219.PubMedCrossRefGoogle Scholar
  7. Battaglia, G., Norman, A.B., Newton, P.L. and I. Creese 1985, In vitro and in vivo irreversible blockade of cortical S2 serotonin receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ): A technique for investigating S2 serotonin receptor recovery, J. Neurochem., (in press).Google Scholar
  8. Battaglia, G., Norman, A.B., Hess, E.J. and Creese, I., 1985, D2 dopamine receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in rat striatum, Neurosci. Letters, 59:177–182.CrossRefGoogle Scholar
  9. Battaglia, G., Norman, A.B., Hess, E.J. and Creese, I., 1985, Functional recovery of D1 dopamine receptor- mediated stimulation of rat striatal adenylate cyclase activity following irreversible receptor blockade, (Submitted).Google Scholar
  10. Belleau, B., Ditullio, V. and Godin, D., 1969, The mechanism of irreversible adrenergic blockade by N-carbethoxy-dihydroquinolines — model studies with typical serine hydrolases, Biochem. Pharm., 18:1039–1044.PubMedCrossRefGoogle Scholar
  11. Belleau, B., Martel, R., Lacasse, G., Menard, M., Weinberg, N.L. and Perron, Y.G., 1969, N-carboxylic acid esters of 1,2 and 1,4-dihydroquinolines. A new class of irreversible inactivators of the catecholamine alpha receptors and potent central nervous system depressants, J. Am. Chem. Soc., 90:823–824.CrossRefGoogle Scholar
  12. Billard, W., Ruperto, V., Crosby, G., Iorio, L.C. and Barnett, A., 1984, Characterization of the binding of [3H]SCH 23390, a selective D1 receptor antagonist ligand, in rat striatum, Life Sci., 35:1885–1893.PubMedCrossRefGoogle Scholar
  13. Boeynaems, J.M. and Dumont, J.E., 1975, Quantitative analysis of the binding of ligands to their receptors, J. Cyclic Nucleotide Res., 1:123–142.Google Scholar
  14. Breese, G.R. and Mueller, R.A., 1985, SCH 23390 antagonism of a D2 dopamine agonist depends upon -catecholaminergic neurons, Eur. J. Pharmacol., 113:109–114.PubMedCrossRefGoogle Scholar
  15. Chang, K.J., Moran, J.F. and Triggle, D.J., 1970, Mechanism of cholinergic antagonism by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), Pharm. Res. Comm., 2:63–66.CrossRefGoogle Scholar
  16. Christensen, A.V., Arnt, J., Hyttel, J., Larsen, J.J. and Svendsen, O., 1984, Pharmacological effects of a specific dopamine D1 antagonist SCH 23390 in comparison with neuroleptics, Life Sci., 34:1529–1540.PubMedCrossRefGoogle Scholar
  17. Creese, I. and Chen, A., 1985, Selective D1 dopamine receptor increase following chronic treatment with SCH 23390, Eur. J. Pharmacol., 109:127–128.PubMedCrossRefGoogle Scholar
  18. Creese, I., Burt, D.R. and Snyder, S.H., 1976, Dopamine. receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs, Science, 192:481–483.PubMedCrossRefGoogle Scholar
  19. Creese, I. and Iversen, S.D., 1975, The pharmacological and anatomical substrates of the amphetamine response in the rat, Brain Res., 83:419–436.PubMedCrossRefGoogle Scholar
  20. Creese, I., Sibley, D.R., Hamblin, M.W. and Leff, S., 1983, The classification of dopamine receptors: relationship to radioligand binding, Ann. Rev. Neurosci., 6:43–71.PubMedCrossRefGoogle Scholar
  21. Cross, A.J., Crow, T.J., Ferrier, I.N., Johnstone, E.C., McCreadie, R.M, Owen, F., Owens, D.G.C. and Poulter, M., 1983, Dopamine receptor changes in schizophrenia in relation to the disease process and movement disorder, J. Neural Transmission Suppl., 18:265–272.Google Scholar
  22. Ezrin-Waters, C. and Seeman, P., 1977, Tolerance to haloperidol catalepsy, Eur. J. Pharmacol., 41:321–327.PubMedCrossRefGoogle Scholar
  23. Fleminger, S., Rupniak, N.M.J., Hall, M.D., Jenner, P. and Marsden, C.D., 1983, Changes in apomorphine-induced stereotypy as a result of subacute neuroleptic treatment correlates with increased D2 receptors, but not with increases in D1 receptors, Biochem. Pharmacol., 32:2921–2927.PubMedCrossRefGoogle Scholar
  24. Hamblin, M.W. and Creese, I., 1983, Behavioral and radioligand binding evidence for irreversible dopamine receptor blockade by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroguinoline, Life Sci., 32:2247–2255.PubMedCrossRefGoogle Scholar
  25. Heidenrich, K.A., Weiland, G.A. and Molinoff, P.B., 1980, Characterization of radiolabeled agonist binding to ß-adrenergic receptors in mammalian tissues, J. Cyclic Nucleotide Res., 6:271–230.Google Scholar
  26. Herrera-Marschitz, M. and Ungerstedt, U., 1984, Evidence that apomorphine and pergolide induce rotation in rats by different actions on D1 and D2 receptor sites, Eur. J. Pharmacol ., 98:165–176.Google Scholar
  27. Herrera-Marschitz, M. and Ungerstedt, U., 1985, Effect of the dopamine D1 antagonist SCH 23390 on rotational behaviour induced by apomorphine and pergolide in 6-hydroxy-dopamine denervated rats, Eur. J. Pharmacol,. 109:349–354.PubMedCrossRefGoogle Scholar
  28. Hess, E.J., Battaglia, G., Norman, A.B. and Creese, I., 1985, In vivo EEDQ specificity for D1 dopamine receptor blockade: Lack of effect on Ns or the catalytic subunit of adenylate cyclase, Soc. for Neurosci.Abstr., 11:313.Google Scholar
  29. Hess, E.J., Battaglia, G., Norman, A.B. and Creese, I., 1985, Differential modification of striatal D1 dopamine receptors and effector moieties by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in vivo and in vitro, (submitted).Google Scholar
  30. Hess, E.J., Battaglia, G., Norman, A.B., Iorio, L.C. and Creese, I., 1985, Guanine nucleotide regulation of agonist interactions at [3H]SCH 23390 labeled D1 dopamine receptors in rat striatum, Eur. J. Pharmacol., in press.Google Scholar
  31. Hoffman, B.B., Michel, T., Brennan, T.B. and Lefkowitz, R.J., 1982, Interactions of agonists with platelet a-2 adrenergic receptors, Endocrinology, 110:926–932.PubMedCrossRefGoogle Scholar
  32. Hoffman, D.C. and Beninger, R.J., 1985, The D1 dopamine receptor antagonist, SCH 23390 reduces locomotor activity and rearing in rats, Pharmacol. Biochem. Beh., 22:341–342.CrossRefGoogle Scholar
  33. Hyttel, J., 1978, Effects of neuroleptics on 3H-haloperidol and 3H-cis(Z)-flupentixol binding and on adenylate cyclase activity in vitro, Life Sci., 23:551–556.PubMedCrossRefGoogle Scholar
  34. Hyttel, J., 1981, Flupentixol and dopamine receptor selectivity, Psychopharmacol., 75:217.CrossRefGoogle Scholar
  35. Hyttel, J., 1984, Functional evidence for selective dopamine D1 receptor blockade by SCH 23390, Neuropharmacol., 23:1395–1401.CrossRefGoogle Scholar
  36. Iorio, L.C, Barnett, A., Leitz, F.H., Houser, V.P. and Korduba, C.A., 1983, SCH23390, a potential benzazepine antipsychotic with unique interactions of dopaminergic systems. J. Pharm. Exp. Ther., 226:462–468.Google Scholar
  37. Jacobs, S. and Cuatrecasas, P., 1976, The mobile receptor hypothesis and cooperativity of hormone binding: application to insulin, Biochem. Biophys. Acta, 433:482–295.PubMedCrossRefGoogle Scholar
  38. Janssen, P.A.J. and Van Brever, W.F.M., 1978, Structure-activity relationships of the butyrophenones and diphenylbutylpiperidines. In: “Handbook of Psychopharmacology”, L.L. Iversen, S.D. Iversen and S.H. Snyder, eds., pp. 1–31, Plenum Press, New York.CrossRefGoogle Scholar
  39. Kebabian, J.W. and Calne, D.B., 1979, Multiple receptors for dopamine, Nature, 277:93–96.PubMedCrossRefGoogle Scholar
  40. Leff, S.E., Hamblin, M.W. and Creese, I. 1985a, Interactions of dopamine agonists with brain D1 receptors labeled by 3H-antagonists: Evidence for the presence of high and low affinity agonist-binding states, Mol. Pharmacol., 27:171–183.PubMedGoogle Scholar
  41. Leff, S.E. and Creese, I., 1985b, Interactions of dopaminergic agonists and antagonists with dopaminergic D3 binding sites in rat striatum: Evidence that [3H]dopamine can label a high affinity agonist-binding state of the D1 dopamine receptor, Mol. Pharmacol., 27:184–192.PubMedGoogle Scholar
  42. Leysen, J.E., Van Gompe, P., Verwimp, M. and Niemegeers, C.J.E., 1983, Role and localization of serotonin-2 (S2) receptor binding sites: effects of neuronal lesions, Advance Biochem. Psychopharmacol., 37:373–383.Google Scholar
  43. Limbird, L.E., 1981, Activation and attenuation of adenylate cyclase: The role of GTP-binding proteins as macromolecular messengers in receptor cyclase coupling, Biochem. J.,194:1–13.Google Scholar
  44. Mailman, R.B., Schulz, D.W., Lewis, M.H., Staples, L., Rollema, H. and Dehaven, D.L., 1984, SCH 23390: A selective D1 dopamine antagonist with potent D2 behavioral actions, Eur. J. Pharmacol., 101:159–160.PubMedCrossRefGoogle Scholar
  45. Meller, E., Bohmaker, K., Goldstein, M. and Friedhoff, A.J., 1985, Inactivation of D1 and D2 dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo: Selective protection by neuroleptics, J. Pharmacol. and Exp. Ther., 233:656–662.Google Scholar
  46. Meller, E., Kuga, S., Friedhoff, A.J. and Goldstein, M., 1985, Selective D2 dopamine receptor agonists prevent catalepsy induced by SCH 23390, a selective D1 antagonist, Life Sci., 36:1857–1864.PubMedCrossRefGoogle Scholar
  47. Molloy, A.G. and Waddington, J.L., 1985, Sniffing, rearing and locomotor responses to the D1 dopamine agonist R-SKF 38393 and to apomorphine: Differential interactions with the selective D1 and D2 antagonists SCH 23390 and metaclopramide, Eur. J. Pharmacol. 108:305–308.PubMedCrossRefGoogle Scholar
  48. O’Boyle, K.M. and Waddington, J.L., 1984, Selective and stereospecific interactions of R-SK&F 38393 with [3H]piflutixol but not [3H]spiperone binding to striatal D1 and D2 dopamine receptors: Comparisons with SCH 23390, Eur. J. Pharmacol., 98:433–436.PubMedCrossRefGoogle Scholar
  49. Onali, P., Olianas, M.C. and Gessa, G.L., 1984, Selective blockade of dopamine D1 receptors by SCH 23390 discloses striatal dopamine D2 receptors mediating the inhibition of adenylate cyclase in rats, Eur. J. Pharmacol., 99:127–128.PubMedCrossRefGoogle Scholar
  50. Plantje, J.F., Hanson, H.A., Davis, F.J. and Stoof, J.C., 1984, The effects of SCH 23390 (+)-YM 09151–2 and (-)-3-PPP and some classical neuroleptics on D1 and D2 receptors in rat neostriatum in vitro, Eur. J. Pharmacol., 105:73–83.PubMedCrossRefGoogle Scholar
  51. Schulz, D.W., Wyrick, S.D. and Mailman, R.B., 1985, [3H]SCH 23390 has the characteristics of a dopamine receptor ligand in the rat central nervous system, Eur. J. Pharmacol., 106:211–212.CrossRefGoogle Scholar
  52. Seamon, K.B., Padagett, W. and Daly, J.W., 1981, Forskolin: Unique diterpine activator of adenylate cyclase in membranes and in intact cells, Proc. Natl. Acad. Sci., 78:3363–3367.PubMedCrossRefGoogle Scholar
  53. Seeman, P., Lee, T., Chau-Wong, M. and Wong, K., 1976, Antipsychotic drug doses and neuroleptic/dopamine receptors, Nature, 261:717–719.PubMedCrossRefGoogle Scholar
  54. Seeman, P., 1981, Brain Dopamine Receptors, Pharmacol. Rev., 32:229–313.Google Scholar
  55. Seeman, P., Ulpian, C., Grigoriadis, D., Pri-Bar, I. and Buchman, O., 1985, Conversion of dopamine D1 receptors from high to low affinity for dopamine, Biochem. Pharmacol., 34:151–154.PubMedCrossRefGoogle Scholar
  56. Setler, P.E., Sarau, H.M., Zirkle, C.L. and Saunders, H.L., 1978, The central effects of a novel dopamine agonist, Eur. J. Pharmacol., 50:419.PubMedCrossRefGoogle Scholar
  57. Sibley, D.R., DeLean, A. and Creese, I., 1982, Anterior pituitary receptors: demonstration of interconvertible high and low affinity states of the D2 dopamine receptor, J. Biol. Chem., 257:6351–6361.PubMedGoogle Scholar
  58. Stoof, J.C. and Kebabian, J.W., 1981, Opposing roles for D1 and D2 dopamine receptors in efflux of cyclic AMP from rat striatum, Nature, 294:366–268.PubMedCrossRefGoogle Scholar
  59. Tarsy, D. and Baldessarini, J., 1974, Behavioural supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines, Neuropharmacol., 13:927–940.CrossRefGoogle Scholar
  60. Tsuruta, K.,Frey, E.A., Grewe, C.W., Cote, T.E., Eskay, R.L. and Kebabian, J.W., 1981, Evidence of LY-141865 specifically stimulates the D2 dopamine receptor, Nature, 292:463–465.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Ellen J. Hess
    • 1
  • Ian Creese
    • 1
  1. 1.Department of NeurosciencesUniversity of CaliforniaSan Diego, La JollaUSA

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