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G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain

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Summary

We detected the existence of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in the striatum of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The level of Gi/Go was significantly decreased by 42% in the putamen of the left hemisphere in schizophrenics; caudate head and globus pallidus levels were unchanged. Decreased Gi or Go may underlie enhanced dopamine function in the schizophrenic brain.

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References

  • Blatt C, Eversole-Cire P, Cohn VH, Zollman S, Fournier REK, Mohandas LT, Nesbitt M, Lugo T, Jones DT, Reed RR, Weiner LP, Sparkes RS, Simon MI (1988) Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human. Proc Natl Acad Sci USA 85: 7642–7646

    Google Scholar 

  • Cortés R, Hökfelt T, Schalling M, Goldstein M, Goldsmith P, Spiegel A, Unson C, Walsh J (1988) Antiserum raised against residues 159–168 of the guanine nucleotide-binding protein Gi3-α reacts with ependymal cells and some neurons in the rat brain containing cholecystokinin- or cholecystokinin- and tyrosine 3-hydroxylase-like immunoreactivities. Proc Natl Acad Sci USA 85: 9351–9355

    Google Scholar 

  • Cross AJ, Crow TJ, Owen F (1981)3H-flupenthixol binding in post-mortem brains of schizophrenics. Evidence for a selective increase in dopamine D2 receptors. Psychopharmacology 74: 122–124

    Google Scholar 

  • Crow TJ (1987) The dopamine hypothesis survives, but there must be a way ahead. Br J Psychiatry 151: 460–465

    Google Scholar 

  • De Armond SJ, Fusco HM, Dewey MM (1976) Structure of the Human Brain, 2nd ed. Oxford University Press

  • Feighner JP, Robins E, Guze SB, Woodruff RA, Winokur G, Munoz R (1972) Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 26: 57–63

    Google Scholar 

  • Feldman AM, Cates AE, Veazey WB, Hershberger RE, Bristow MR, Baughman KL, Baumgartner WA, Van Dop C (1988) Increase of the 40,000-mol wt pertussis toxin (G protein) in the failing human heart. J Clin Invest 82: 189–197

    Google Scholar 

  • Gilman AG (1984) G proteins and dual control of adenylate cyclase. Cell 36: 577–579

    Google Scholar 

  • Graziano MP, Gilman AG (1987) Guanine nucleotide-binding regulatory proteins. Mediators of transmembrane signaling. Trends Pharmacol Sci 8: 478–481

    Google Scholar 

  • Iyengar R, Rich KA, Herberg JT, Grenet D, Mumby S, Codina J (1987) Identification of a new GTP-binding protein. A Mr = 43,000 substrate for pertussis toxin. J Biol Chem 262: 9239–9245

    Google Scholar 

  • Katada T, Ui M (1982) Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc Natl Acad Sci USA 79: 3129–3133

    Google Scholar 

  • Katada T, Oinuma M, Ui M (1986) Two guanine nucleotide-binding proteins in rat brain serving as the specific substrate of islet-activating protein, pertussis toxin. Interaction of the α-subunits with βγ-subunits in development of their biological activities. J Biol Chem 261: 8182–8191

    Google Scholar 

  • Katada T, Oinuma M, Kusakabe K, Ui M (1987) A new GTP-binding protein in brain tissues serving as the specific substrate of islet-activating protein, pertussis toxin. FEBS Lett 213: 353–358

    Google Scholar 

  • Kety SS (1959) Biochemical theories of schizophrenia. Part I of a two-part critical review of current theories and of the evidence used to support them. Science 129: 1528–1532

    Google Scholar 

  • Lee T, Seeman P, Tourtellotte WW, Farley U, Hornykeiwicz O (1978) Binding of3H-neuroleptics and3H-apomorphine in schizophrenic brains. Nature 274: 897–900

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  • Mackay AVP, Iversen LL, Rossor M, Spokes E, Bird E, Arregui A, Creese I, Snyder SH (1982) Increased brain dopamine and dopamine receptors in schizophrenia. Arch Gen Psychiatry 39: 991–997

    Google Scholar 

  • Memo M, Lovenberg W, Hanbauer I (1982) Agonist-induced subsensitivity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum. Proc Natl Acad Sci USA 79: 4456–4460

    Google Scholar 

  • Memo M, Kleinman JE, Hanbauer I (1983) Coupling of dopamine D1 recognition sites with adenylate cyclase in nuclei accumbens and caudatus of schizophrenics. Science 221: 1304–1307

    Google Scholar 

  • Neumann J, Schmitz W, Scholz H, von Meyerinck L, Doring V, Kalmar P (1988) Increase in myocardial Gi-proteins in heart failure. Lancet ii: 936–937

    Google Scholar 

  • Owen F, Cross AJ, Crow TJ, Longden A, Poulter M, Riley GJ (1978) Increased dopaminereceptor sensitivity in schizophrenia. Lancet ii: 223–226

    Google Scholar 

  • Owens DGC, Johnstone EC, Frith CD (1982) Spontaneous involuntary disorders of movement. Their prevalence, severity, and distribution in chronic schizophrenics with and without treatment with neuroleptics. Arch Gen Psychiatry 39: 452–461

    Google Scholar 

  • Randrup A, Munkvad I (1967) Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia 11: 300–310

    Google Scholar 

  • Reynolds GP (1983) Increased concentrations and lateral asymmetry of amygdala dopamine in schizophrenia. Nature 305: 527–529

    Google Scholar 

  • Reynolds GP, Czudek C, Bzowej N, Seeman P (1987) Dopamine receptor asymmetry in schizophrenia. Lancet i: 979

    Google Scholar 

  • Roberts GW, Colter N, Lofthouse R, Johnstone EC, Crow TJ (1987) Is there gliosis in schizophrenia? Investigation of the temporal lobe. Biol Psychiatry 22: 1459–1468

    Google Scholar 

  • Roberts GW, Bruton CJ (1989) Notes from the graveyard. Neuropathology and schizophrenia. Annotation for Neuropathology and Applied Neurobiology (in press)

  • Sasaki K, Sato M (1987) A single GTP-binding protein regulates K+-channels coupled with dopamine, histamine and acetylcholine receptors. Nature 325: 259–262

    Google Scholar 

  • Snyder SH, Banerjee SP, Yamamura HI, Greenberg D (1974) Drugs, neurotransmitters, and schizophrenia. Phenothiazines, amphetamines, and enzymes synthesizing psychotomimetic drugs and schizophrenia research. Science 184: 1243–1253

    Google Scholar 

  • Spiegel AM, Gierschik P, Levine MA, Downs RW (1985) Clinical implications of guanine nucleotide-binding proteins as receptor-effect or couplers. N Engl J Med 312: 26–33

    Google Scholar 

  • Stoof JC, Kebabian JW (1981) Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 294: 366–368

    Google Scholar 

  • Suki WN, Abramowitz J, Mattera R, Codina J, Birnbaumer L (1987) The human genome encodes at least three non-allellic G proteins with α1-type subunits. FEBS Lett 220: 187–192

    Google Scholar 

  • Ui M (1984) Islet-activating protein, pertussis toxin. A probe for functions of the inhibitory guanine nucleotide regulatory component of adenylate cyclase. Trends Pharmacol Sci 5: 277–279

    Google Scholar 

  • Wing JK, Cooper JE, Sartorius N (1974) Measurement and Classification of Psychiatric Symptoms. London

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Okada, F., Crow, T.J. & Roberts, G.W. G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain. J. Neural Transmission 79, 227–234 (1990). https://doi.org/10.1007/BF01245133

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  • DOI: https://doi.org/10.1007/BF01245133

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