Advertisement

Quantitative Assay of Dopamine Receptor Subtypes

  • Rita M. Huff
  • Perry B. Molinoff
Part of the New Horizons in Therapeutics book series (NHTH)

Abstract

Dopamine, acting as a neurotransmitter in the central nervous system, is involved in the regulation of a variety of behaviors in man and animals. Studies carried out over the last decade have shown that not all of the responses attributed to the release of dopamine are mediated through the same kind of receptor. Cools and Van Rossum (1976) first proposed the existence of two types of receptors for dopamine in an attempt to explain results obtained in studies of the effects of dopamine and apomorphine on stereotypy and locomotor activity. However, precise pharmacological characterization of receptors is difficult if only behavioral models are utilized. Biochemical studies have shown that stimulation of dopamine receptors can result, in some tissues, in an increase in the accumulation of cyclic AMP through activation of dopamine-sensitive adenylate cyclase (Kebabian and Greengard, 1971). Not all dopamine receptors, however, appear to act through increases in cyclic AMP levels.

Keywords

Frontal Cortex Dopamine Receptor Guanine Nucleotide Adenylate Cyclase Activity Hill Coefficient 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Boeynaems, J. M., and Dumont, J. E., 1977, The two-step model of ligand-receptor interaction, Mol. Cell. Endocrinol. 7:33–47.PubMedCrossRefGoogle Scholar
  2. Brown, E. M., Carroll, R. J., and Aurbach, G. D., 1977, Dopaminergic Stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells, Proc. Natl. Acad. Sci. U.S.A. 74:4210–4213.PubMedCrossRefGoogle Scholar
  3. Cheng, Y-C, and Prusoff, W. H., 1973, Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 percent inhibition (I50) of an enzymatic reaction, Biochem. Pharmacol. 22:3099–3108.PubMedCrossRefGoogle Scholar
  4. Clement-Cormier, Y. C, Kebabian, J. W., Petzold, G. L., and Greengard, P., 1974, Dopamine-sensitive adenylate cyclase in mammalian brain: A possible site of action of antipsychotic drugs, Proc. Natl. Acad. Sci. U.S.A. 71:1113–1117.PubMedCrossRefGoogle Scholar
  5. Cools, A. R., and Van Rossam, J. M., 1976, Excitation-mediating and inhibition-mediating dopamine-reeeptors: A new coneept towards a better understanding of electrophysiological, biochemical, pharmacological, functional, and clinical data, Psychopharmacologia 45:243–254.PubMedCrossRefGoogle Scholar
  6. Creese, I., Stewart, K., and Snyder, S. H., 1979, Species variations in dopamine receptor binding, Eur. J. Pharmacol. 60:55–66.PubMedCrossRefGoogle Scholar
  7. Cross, A. J., and Owen, F., 1980, Characteristics of 3H-cis-flupenthixol binding to calf brain membranes, Eur. J. Pharmacol. 65:341–347.PubMedCrossRefGoogle Scholar
  8. De Lean, A., Stadel, J. M., and Lefkowitz, R. J., 1980, A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled β-adrenergic receptor, J. Biol. Chem. 255:7108–7117.PubMedGoogle Scholar
  9. De Lean, A., Kilpatrick, B. F., and Caron, M. G., 1982, Guanine nucleotides regulate both dopaminergic agonist and antagonist binding in porcine anterior pituitary, Endocrinology 110:1064–1066.PubMedCrossRefGoogle Scholar
  10. Hegstrand, L. R., Minneman, K. P., and Molinoff, P. B., 1979, Multiple effects of guanosine triphosphate on beta adrenergic receptors and adenylate cyclase activity in rat heart, lung and brain, J. Pharmacol. Exp. Ther. 210:215–221.Google Scholar
  11. Hofstee, B. H. J., 1952, On the evaluation of the constants Vm and Km in enzyme reactions, Science 116:329–331.PubMedCrossRefGoogle Scholar
  12. Huff, R. M., and Molinoff, P. B., 1982, Quantitative determination of dopamine receptor Subtypes not linked to activation of adenylate cyclase in rat striatum, Proc. Natl. Acad. Sei. U.S.A. 79:7561–7565.CrossRefGoogle Scholar
  13. Hyttel, J., 1978, Effects of neuroleptics on 3H-haloperidol and 3H-cis(Z)-flupenthixol binding and on adenylate cyclase activity in vitro, Life Sci. 23:551–556.PubMedCrossRefGoogle Scholar
  14. Kebabian, J. W., and Calne, D. B., 1979, Multiple receptors for dopamine, Nature 277:93–96.PubMedCrossRefGoogle Scholar
  15. Kebabian, J. W., and Greengard, P., 1971, Dopamine-sensitive adenyl cyclase: Possible role in synaptic transmission, Science 174:1346–1349.PubMedCrossRefGoogle Scholar
  16. Kebabian, J. W., Petzold, G. L., and Greengard, P., 1972, Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor,” Proc. Natl. Acad. Sci. U.S.A. 69:2145–2149.PubMedCrossRefGoogle Scholar
  17. Krueger, B. K., Forn, J., Walters, J. R., Roth, R. H., and Greengard, P., 1976, Stimulation by dopamine of adenosine cyclic 3’,5’-monophosphate formation in rat caudate nucleus: Effect of lesions of the nigro-neostriatal pathway, Mol. Pharmacol. 12:639–648.PubMedGoogle Scholar
  18. Laduron, P. M., and Leysen, J. E., 1979, Domperidone, a specific in vitro dopamine antagonist, devoid of in vivo central dopaminergic activity, Biochem. Pharmacol. 28:2161–2165.PubMedCrossRefGoogle Scholar
  19. Lefkowitz, R. J., Mullikin, D., Wood, C. L., Gore, T. B., and Mukherjee, C, 1977, Regulation of Prostaglandin receptors by Prostaglandins and guanine nucleotides in frog erythrocytes, J. Biol. Chem. 252:5295–5303.PubMedGoogle Scholar
  20. Leysen, J. E., Gommeren, W., and Laduron, P. M., 1978a, Spiperone: A ligand of choice for neuroleptic receptors. I. Kinetics and characteristics of in vitro binding, Biochem. Pharmacol. 27:307–316.CrossRefGoogle Scholar
  21. Leysen, J. E., Niemegeers, C. J. E., Tollenaere, J. P., and Laduron, P. M., 1978b, Serotonergic component of neuroleptic receptors, Nature 272:168–171.CrossRefGoogle Scholar
  22. Leysen, J. E., Awouters, F., Kennis, L., Laduron, P. M., Vandenberk, J., and Janssen, P. A. J., 1981, Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors, Life Sci. 28:1015–1022.PubMedCrossRefGoogle Scholar
  23. List, S. J., and Seeman, P., 1981, Resolution of dopamine and Serotonin receptor components of [3H]spiperone binding to rat brain regions, Proc. Natl. Acad. Sci. U.S.A. 78:2620–2624.PubMedCrossRefGoogle Scholar
  24. List, S. J., and Seeman, P., 1982, [3H]-Dopamine labeling of D3 dopaminergic sites in human, rat, and calf brain, J. Neurochem. 39:1363–1373.PubMedCrossRefGoogle Scholar
  25. Maguire, M. E., Van Arsdale, P. M., and Gilman, A. G., 1976, An agonist-specific effect of guanine nucleotides on binding to the beta adrenergic receptor, Mol. Pharmacol. 12:335–339.PubMedGoogle Scholar
  26. Maguire, M. E., Ross, E. M., and Gilman, A. G., 1977, β-Adrenergic receptor: Ligand binding properties and the interaction with adenylyl cyclase, Adv. Cyclic Nucleotide Res. 8:1–83.PubMedGoogle Scholar
  27. Marchais, D., and Bockaert, J., 1980, Is there a connection between high affinity [3H]-spiperone binding sites and DA-sensitive adenylate cyclase in corpus striatum?, Biochem. Pharmacol. 29:1331–1336.PubMedCrossRefGoogle Scholar
  28. Marchais, D., Tassin, J. P., and Bockaert, J., 1980, Dopaminergic component of [3H]spiroperidol binding in the rat anterior cerebral cortex, Brain Res. 183:235–240.PubMedCrossRefGoogle Scholar
  29. Martres, M.-P., Baudry, M., and Schwartz, J.-C, 1978, Characterization of 3H-domperidone binding on striatal dopamine receptors, Life Sci. 23:1781–1784.PubMedCrossRefGoogle Scholar
  30. Miller, R. J., Horn, A. S., and Iversen, L. L., 1974, The action of neuroleptic drugs on dopamine-stimulated adenosine cyclic 3’,5’-monophosphate production in rat neostriatum and limbic forebrain, Mol. Pharmacol. 10:759–766.Google Scholar
  31. Minneman, K. P., Hegstrand, L. R., and Molinoff, P. B., 1979, Simultaneous determination of beta-1 and beta-2-adrenergic receptors in tissues containing both receptor subtypes, Mol. Pharmacol. 16:34–46.PubMedGoogle Scholar
  32. Minneman, K. P., Pittman, R. N., and Molinoff, P. B., 1981, β-Adrenergic receptor Subtypes: Properties, distribution, and regulation, Annu. Rev. Neurosci. 4:419–461.PubMedCrossRefGoogle Scholar
  33. Molinoff, P. B., Wolfe, B. B., and Weiland, G. A., 1981, Quantitative analysis of drug receptor interactions. II. Determination of the properties of receptor subtypes, Life Sci. 29:427–443.PubMedCrossRefGoogle Scholar
  34. Munemura, M., Cote, T. E., Tsuruta, K., Eskay, R. L., and Kebabian, J. W., 1980, The dopamine receptor in the intermediate lobe of the rat pituitary gland: Pharmacological characterization, Endocrinology 107:1676–1683.PubMedCrossRefGoogle Scholar
  35. Pedigo, N. W., Reisine, T. K., Fields, J. Z., and Yamamura, H. I., 1978, 3H-Spiroperidol binding to two receptor sites in both the corpus striatum and frontal cortex, Eur. J. Pharmacol. 50:451–453.PubMedCrossRefGoogle Scholar
  36. Rappaport, R. S., and Grant, N. H., 1974, Growth hormone releasing factor of microbial origin, Nature 248:73–75.PubMedCrossRefGoogle Scholar
  37. Rodbell, M., Krans, H. M. J., Pohl, S. L., and Birnbaumer, L., 1971, The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. IV. Effects of guanyl nucleotides on binding of (125I)-glucagon, J. Biol. Chem. 246:1872–1876.PubMedGoogle Scholar
  38. Rzezniczak, H. W., Gundlach, A. L., and Beart, P. M., 1982, Labelling of high (D-2 receptor) and low affinity sites by [3H]domperidone in homogenates of the corpus striatum of the rat, Neurosci. Lett. 30:63–68.PubMedCrossRefGoogle Scholar
  39. Scatchard, G., 1949, The attractions of proteins for small molecules and ions, Ann. N.Y. Acad. Sci. 51:660–671.CrossRefGoogle Scholar
  40. Schwarcz, R., Creese, I., Coyle, J. T., and Snyder, S. H., 1978, Dopamine receptors localised on cerebral cortical afferents to rat corpus striatum, Nature 271:766–768.PubMedCrossRefGoogle Scholar
  41. Seeman, P., 1977, Anti-schizophrenic drugs—membrane receptor sites of action, Biochem. Pharmacol. 26:1741–1748.PubMedCrossRefGoogle Scholar
  42. Seeman, P., 1980, Brain dopamine receptors, Pharmacol. Rev. 32:229–313.PubMedGoogle Scholar
  43. Sibley, D. R., and Creese, I., 1980, Dopamine receptor binding in bovine intermediate lobe pituitary membranes, Endocrinology 107:1405–1409.PubMedCrossRefGoogle Scholar
  44. Sokoloff, P., Martres, M. P., and Schwartz, J. C, 1980, Three classes of dopamine receptor (D-2, D-3, D-4) identified by binding studies with 3H-apomorphine and 3H-domperidone, Naunyn Schmiedebergs Arch. Pharmacol. 315:89–102.PubMedCrossRefGoogle Scholar
  45. Wolfe, B. B., and Harden, T. K., 1981, Guanine nucleotides modulate the affinity of antagonists at β-adrenergic receptors, J. Cyclic Nucleotide Res. 7:303–312.PubMedGoogle Scholar
  46. Zahniser, N. R., and Molinoff, P. B., 1978, Effect of guanine nucleotides on striatal dopamine receptors, Nature 275:453–455.PubMedCrossRefGoogle Scholar
  47. Zahniser, N. R., Heidenreich, K. A., and Molinoff, P. B., 1981, Binding of [3H]amino-6,7-dihydroxy-l,2,3,4-tetrahydronaphthalene to rat striatal membranes. Effects of purine nucleotides and ultraviolet irradiation, Mol. Pharmacol. 19:372–378.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Rita M. Huff
    • 1
  • Perry B. Molinoff
    • 1
  1. 1.Department of PharmacologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations