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. 1977 Mar;74(3):1242–1244. doi: 10.1073/pnas.74.3.1242

Quantitative correlation of dopamine-dependent adenylate cyclase with responses to levodopa in various mice.

L C Tang, G C Cotzias
PMCID: PMC430659  PMID: 265566

Abstract

We obtained 12 groups of mice with widely different neurological responses to levodopa by selecting them from different strains and submitting some of them to pretreatments. We scored the symptoms evoked by a standardized dose of levodopa in one subgroup from each group. We tested another subgroup for activation of an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by a standardized dose of dopamine added to homogenates of the caudate nuclei of the brains of these mice. Both sets of tests were performed randomly. When the accruing two sets of data were plotted against each other there emerged a straight line which fitted the data with a coefficient of correlation of 0.97 (P less than 0.0001). The dopamine-dependent activity of the adenylate cyclase of the brain was thus shown to be a determinant of the neurological responses of intact animals to a dopaminergic drug.

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Selected References

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

  1. 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]
  2. Clement-Cormier Y. C., Parrish R. G., Petzold G. L., Kerabian J. W., Greengard P. Characterization of a dopamine-sensitive adenylate cyclase in the rat caudate nucleus. J Neurochem. 1975 Aug;25(2):143–149. doi: 10.1111/j.1471-4159.1975.tb12241.x. [DOI] [PubMed] [Google Scholar]
  3. Cotzias G. C., Tang L. C., Mena I. Effects of inhibitors and stimulators of protein synthesis on the cerebral actions of L-dopa. Neurosci Res (N Y) 1973;5(0):97–108. doi: 10.1016/b978-0-12-512505-5.50011-2. [DOI] [PubMed] [Google Scholar]
  4. Cotzias G. C., Tang L. C., Miller S. T., Sladic-Simic D., Hurley L. S. A mutation influencing the transportation of manganese, L-dopa, and L-tryptophan. Science. 1972 Apr 28;176(4033):410–412. doi: 10.1126/science.176.4033.410. [DOI] [PubMed] [Google Scholar]
  5. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Horn A. S., Cuello A. C., Miller R. J. Dopamine in the mesolimbic system of the rat brain: endogenous levels and the effects of drugs on the uptake mechanism and stimulation of adenylate cyclase activity. J Neurochem. 1974 Feb;22(2):265–270. doi: 10.1111/j.1471-4159.1974.tb11589.x. [DOI] [PubMed] [Google Scholar]
  7. Karobath M., Leitich H. Antipsychotic drugs and dopamine-stimulated adenylate cyclase prepared from corpus striatum of rat brain. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2915–2918. doi: 10.1073/pnas.71.7.2915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Kebabian J. W., Saavedra J. M. Dopamine-sensitive adenylate cyclase occurs in a region of substantia nigra containing dopaminergic dendrites. Science. 1976 Aug 20;193(4254):683–685. doi: 10.1126/science.181842. [DOI] [PubMed] [Google Scholar]
  10. Seeman P., Lee T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science. 1975 Jun 20;188(4194):1217–1219. doi: 10.1126/science.1145194. [DOI] [PubMed] [Google Scholar]
  11. Tang L. C., Cotzias G. C., Dunn M. Changing the actions of neuroactive drugs by changing brain protein synthesis. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3350–3354. doi: 10.1073/pnas.71.9.3350. [DOI] [PMC free article] [PubMed] [Google Scholar]

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