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. 1982 Jul;79(14):4456–4460. doi: 10.1073/pnas.79.14.4456

Agonist-induced subsensitivity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum.

M Memo, W Lovenberg, I Hanbauer
PMCID: PMC346691  PMID: 6956874

Abstract

Incubation, for 30 min, of striatal slices with 10 microM dopamine, 10 microM apomorphine, or 10 microM SKF 38393 decreased dopamine-stimulated adenylate cyclase activity by 50-60%. This loss in dopamine-stimulated enzyme activity appears to be mediated by a persistent occupancy of recognition sites of the D-1 receptor because: (i) at 10 microM, SKF 38393, a selective D-1 receptor agonist, facilitates desensitization and Ly 141865, a selective D-2 receptor agonist, fails to elicit desensitization of dopamine-dependent adenylate cyclase; and (ii) preincubation with dopamine in the presence of 1 microM haloperidol but not 1 microM sulpiride curtails the desensitization of dopamine-dependent adenylate cyclase. In dopamine-desensitized striatal slices of the Kd for N-propylnorapomorphine binding is increased but the content of membrane-bound calmodulin and the activation of adenylate cyclase by NaF and cholera toxin are decreased significantly. In striatal slices incubated with dopamine for prolonged time periods the coupling of the GTP-binding protein with adenylate cyclase and dopamine recognition sites may be impaired and the content of membrane-bound calmodulin is decreased.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burt D. R., Creese I., Snyder S. H. Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science. 1977 Apr 15;196(4287):326–328. doi: 10.1126/science.847477. [DOI] [PubMed] [Google Scholar]
  2. Butcher F. R. A rapid filter paper disk assay for picomole amounts of cyclic AMP using a cyclic AMP dependent protein kinase. Horm Metab Res. 1971 Sep;3(5):336–340. doi: 10.1055/s-0028-1094138. [DOI] [PubMed] [Google Scholar]
  3. Cassel D., Selinger Z. Mechanism of adenylate cyclase activation through the beta-adrenergic receptor: catecholamine-induced displacement of bound GDP by GTP. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4155–4159. doi: 10.1073/pnas.75.9.4155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chuang D. M., Kinnier W. J., Farber L., Costa E. A biochemical study of receptor internalization during beta-adrenergic receptor desensitization in frog erythrocytes. Mol Pharmacol. 1980 Nov;18(3):348–355. [PubMed] [Google Scholar]
  5. Clement-Cormier Y. C., Kebabian J. W., Petzold G. L., Greengard P. Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1113–1117. doi: 10.1073/pnas.71.4.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Creese I., Padgett L., Fazzini E., Lopez F. 3H-N-n-propylnorapomorphine: a novel agonist ligand for central dopamine receptors. Eur J Pharmacol. 1979 Jul 1;56(4):411–412. doi: 10.1016/0014-2999(79)90274-7. [DOI] [PubMed] [Google Scholar]
  7. Creese I., Prosser T., Synder S. H. Dopamine receptor binding: specificity, localization and regulation by ions and guanyl nucleotides. Life Sci. 1978 Aug 7;23(5):495–499. doi: 10.1016/0024-3205(78)90160-1. [DOI] [PubMed] [Google Scholar]
  8. Creese I., Usdin T. B., Snyder S. H. Dopamine receptor binding regulated by guanine nucleotides. Mol Pharmacol. 1979 Jul;16(1):69–76. [PubMed] [Google Scholar]
  9. Gill D. M., Meren R. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3050–3054. doi: 10.1073/pnas.75.7.3050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gnegy M. E., Nathanson J. A., Uzunov P. Release of the phosphodiesterase activator by cyclic AMP-dependent ATP:protein phosphotransferase from subcellular fractions of rat brain. Biochim Biophys Acta. 1977 Mar 29;497(1):75–85. doi: 10.1016/0304-4165(77)90140-4. [DOI] [PubMed] [Google Scholar]
  11. Gnegy M., Uzunov P., Costa E. Participation of an endogenous Ca++-blinding protein activator in the development of drug-induced supersensitivity of striatal dopamine receptors. J Pharmacol Exp Ther. 1977 Sep;202(3):558–564. [PubMed] [Google Scholar]
  12. Hanbauer I., Gimble J., Lovenberg W. Changes in soluble calmodulin following activation of dopamine receptors in rat striatal slices. Neuropharmacology. 1979 Nov;18(11):851–857. doi: 10.1016/0028-3908(79)90081-9. [DOI] [PubMed] [Google Scholar]
  13. Hanbauer I., Pradhan S., Yang H. Y. Role of calmodulin in dopaminergic transmission. Ann N Y Acad Sci. 1980;356:292–303. doi: 10.1111/j.1749-6632.1980.tb29619.x. [DOI] [PubMed] [Google Scholar]
  14. Harden T. K., Su Y. F., Perkins J. P. Catecholamine-induced desensitization involves an uncoupling of beta-adrenergic receptors and adenylate cyclase. J Cyclic Nucleotide Res. 1979;5(2):99–106. [PubMed] [Google Scholar]
  15. Homburger V., Lucas M., Cantau B., Barabe J., Penit J., Bockaert J. Further evidence that desensitization of beta-adrenergic-sensitive adenylate cyclase proceeds in two steps. Modification of the coupling and loss of beta-adrenergic receptors. J Biol Chem. 1980 Nov 10;255(21):10436–10444. [PubMed] [Google Scholar]
  16. Kebabian J. W., Calne D. B. Multiple receptors for dopamine. Nature. 1979 Jan 11;277(5692):93–96. doi: 10.1038/277093a0. [DOI] [PubMed] [Google Scholar]
  17. Kebabian J. W., Petzold G. L., Greengard P. Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the "dopamine receptor". Proc Natl Acad Sci U S A. 1972 Aug;69(8):2145–2149. doi: 10.1073/pnas.69.8.2145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Memo M., Pradhan S., Hanbauer I. Cocaine-induced supersensitivity of striatal dopamine receptors: role of endogenous calmodulin. Neuropharmacology. 1981 Dec;20(12A):1145–1150. doi: 10.1016/0028-3908(81)90055-1. [DOI] [PubMed] [Google Scholar]
  20. Minneman K. P., Quik M., Emson P. C. Receptor-linked cyclic AMP systems in rat neostriatum: differential localization revealed by kainic acid injection. Brain Res. 1978 Aug 11;151(3):507–521. doi: 10.1016/0006-8993(78)91083-1. [DOI] [PubMed] [Google Scholar]
  21. Perkins J. P., Johnson G. L., Harden T. K. Drug-induced modification of the responsiveness of adenylate cyclase to hormones. Adv Cyclic Nucleotide Res. 1978;9:19–32. [PubMed] [Google Scholar]
  22. Pfeuffer T. GTP-binding proteins in membranes and the control of adenylate cyclase activity. J Biol Chem. 1977 Oct 25;252(20):7224–7234. [PubMed] [Google Scholar]
  23. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  24. Scatton B., Bischoff S., Dedek J., Korf J. Regional effects of neuroleptics on dopamine metabolism and dopamine-sensitive adenylate cyclase activity. Eur J Pharmacol. 1977 Aug 15;44(4):287–292. doi: 10.1016/0014-2999(77)90301-6. [DOI] [PubMed] [Google Scholar]
  25. Seeman P. Brain dopamine receptors. Pharmacol Rev. 1980 Sep;32(3):229–313. [PubMed] [Google Scholar]
  26. Shear M., Insel P. A., Melmon K. L., Coffino P. Agonist-specific refractoriness induced by isoproterenol. Studies with mutant cells. J Biol Chem. 1976 Dec 10;251(23):7572–7576. [PubMed] [Google Scholar]
  27. Spiegel A. M., Downs R. W., Jr, Aurbach G. D. Separation of a guanine nucleotide regulatory unit from the adenylate cyclase complex with GTP affinity chromatography. J Cyclic Nucleotide Res. 1979;5(1):3–17. [PubMed] [Google Scholar]
  28. Su Y. F., Harden T. K., Perkins J. P. Catecholamine-specific desensitization of adenylate cyclase. Evidence for a multistep process. J Biol Chem. 1980 Aug 10;255(15):7410–7419. [PubMed] [Google Scholar]
  29. Su Y. F., Harden T. K., Perkins J. P. Isoproterenol-induced desensitization of adenylate cyclase in human astrocytoma cells. Relation of loss of hormonal responsiveness and decrement in beta-adrenergic receptors. J Biol Chem. 1979 Jan 10;254(1):38–41. [PubMed] [Google Scholar]
  30. Terasaki W. L., Brooker G., de Vellis J., Inglish D., Hsu C. Y., Moylan R. D. Involvement of cyclic amp and protein synthesis in catecholamine refractoriness. Adv Cyclic Nucleotide Res. 1978;9:33–52. [PubMed] [Google Scholar]
  31. Trabucchi M., Longoni R., Fresia P., Spano P. F. Sulpiride: a study of the effects on dopamine receptors in rat neostriatum and limbic forebrain. Life Sci. 1975 Nov 15;17(10):1551–1556. doi: 10.1016/0024-3205(75)90176-9. [DOI] [PubMed] [Google Scholar]
  32. Tsuruta K., Frey E. A., Grewe C. W., Cote T. E., Eskay R. L., Kebabian J. W. Evidence that LY-141865 specifically stimulates the D-2 dopamine receptor. Nature. 1981 Jul 30;292(5822):463–465. doi: 10.1038/292463a0. [DOI] [PubMed] [Google Scholar]

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