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Reduced concentrations of the α-subunit of GTP-binding protein Go in schizophrenic brain

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Summary

Concentrations of the α-subunits of GTP-binding protein, Go (Goα) and of Gi 2 (Gi 2α) in 6 areas (the hippocampus, parahippocampus, putamen, caudate head, orbital frontal cortex, and lateral temporal cortex) of control and schizophrenic postmortem brains were investigated using the highly sensitive enzyme immunoassay method. There was a significant decrease in Goα in the hippocampus and caudate head of the right hemisphere in schizophrenic patients compared to controls; the ANOVA (a general linear model; SAS Type II) demonstrated a significant diagnosis × side interaction only in the hippocampus. In other areas of the brain, analysis by grouping under diagnosis, side, age, gender, and postmortem delay showed no significant deviations in Goα between controls and schizophrenics. The concentrations of Gi 2α did not differ significantly in any area. These findings contrasted with the results yielded by ADP-ribosylation, which showed decreased pertussis toxin ADP-ribosylated amounts in the hippocampus and putamen of the contralateral (left) hemisphere. Some abnormal receptor — Go or Gi 1 signalling in hippocampus, putamen or caudate head may be involved in the pathogenesis of schizophrenia.

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References

  • Asano T, Ui M, Ogasawara N (1985) Prevention of the agonist binding to γ-aminobutyric acid B receptors by guanine nucleotides and islet-activating protein, pertussis toxin, in bovine cerebral cortex: possible coupling of the toxin-sensitive GTP-binding proteins to receptors. J Biol Chem 260: 12653–12658

    Google Scholar 

  • Asano T, Semba R, Ogasawara N, Kato K (1987) Highly sensitive immunoassay for the α-subunit of the GTP-binding protein Go and its regional distribution in bovine brain. J Neurochem 48: 1617–1623

    Google Scholar 

  • Asano T, Semba R, Kamiya N, Ogasawara N, Kato K (1988) Go, a GTP-binding protein: immunochemical and immunohistochemical localization in the rat. J Neurochem 50: 1164–1169

    Google Scholar 

  • Asano T, Morishita R, Semba R, Itoh H, Kaziro Y, Kato K (1989) Identification of lung major GTP-binding protein as Gi 2 and its distribution in various rat tissues determined by immunoassay. Biochemistry 28: 4749–4754

    Google Scholar 

  • Asano T, Shinohara H, Morishita R, Kato K (1990) Immunochemical and immunohistochemical localization of the G protein Gi 1 in rat central nervous tissues. J Biochem 108: 988–994

    Google Scholar 

  • Bogerts B, Meertz E, Schonfeldt-Bausch R (1985) Basal ganglia and limbic system pathology in schizophrenia: a morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 42: 784–791

    Google Scholar 

  • Brown R, Colter N, Corsellis JAN, Crow TJ, Frith CD, Jagoe R, Johnstone EC, Marsh L (1986) Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder. Arch Gen Psychiatry 43: 36–42

    Google Scholar 

  • Crow TJ, Ball J, Bloom SR, Brown R, Bruton CJ, Colter N, Frith CD, Johnstone EC, Owens DGC, Roberts GW (1989) Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. Arch Gen Psychiatry 46: 1145–1150

    Google Scholar 

  • Deakin JFW, Slater P, Simpsom MDC, Gilchrist AC, Skan WJ, Royston MC, Reynolds GP, Cross AJ (1989) Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia. J Neurochem 52: 1781–1786

    Google Scholar 

  • 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 

  • Florio VA, Sternweis PC (1985) Reconstitution of resolved muscarinic cholinergic receptors with purified GTP-binding proteins. J Biol Chem 260: 3477–3483

    Google Scholar 

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

    Google Scholar 

  • Gilman AG (1987) G-proteins: transducers of receptor-generated signals. Annu Rev Biochem 56: 615–649

    Google Scholar 

  • Itoh H, Kozasa T, Nagata S, Nakamura S, Katada T, Ui M, Iwai S, Ohtsuka E, Kawasaki H, Suzuki K, Kaziro Y (1986) Molecular cloning and sequence determination of cDNAs for α-subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain. Proc Natl Acad Sci USA 83: 3776–3780

    Google Scholar 

  • Jakob H, Beckmann H (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65: 303–326

    Google Scholar 

  • Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L (1976) Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet ii: 924–926

    Google Scholar 

  • Kerwin RW, Patel S, Meldrum BS, Czudek C, Reynolds GP (1988) Asymmetrical loss of glutamate receptor subtype in left hippocampus in schizophrenia. Lancet i: 583–584

    Google Scholar 

  • Kikuchi A, Kozawa O, Kaibuchi K, Katada T, Ui M, Takai Y (1986) Direct evidence for involvement of a guanine nucleotide-binding protein in chemotactic peptide-stimulated formation of inositol biphosphate and triphosphate in differentiated human leukemic (HL-60) cells. J Biol Chem 261: 11558–11562

    Google Scholar 

  • Kim MH, Neubig RR (1987) Membrane reconstitution of high-affinity α2 adrenergic agonist binding with guanine nucleotide regulatory proteins. Biochemistry 26: 3664–3672

    Google Scholar 

  • Kurose H, Katada T, Haga T, Haga K, Ichiyama A, Ui M (1986) Functional interaction of purified muscarinic receptors with purified inhibitory guanine nucleotide regulatory proteins reconstituted in phospholipid vesicles. J Biol Chem 61: 6423–6428

    Google Scholar 

  • Lesch A, Bogerts B (1984) The diencephalon in schizophrenia: evidence for reduced thickness of the periventricular grey matter. Eur Arch Psychiat Neurol Sci 234: 212–219

    Google Scholar 

  • Manji HK (1992) G-proteins: implications for psychiatry. Am J Psychiatry 149: 746–760

    Google Scholar 

  • Morishita R, Kato K, Asano T (1988) Major pertussis-toxin-sensitive GTP-binding protein of bovine lung. Purification, characterization, and production of specific antibodies. Eur J Biochem 174: 87–94

    Google Scholar 

  • Nishimoto I, Okamoto T, Matsuura Y, Takahashi S, Okamoto T, Murayama Y, Ogata E (1993) Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go. Nature 362: 75–79

    Google Scholar 

  • Nishino K, Kitamura N, Hashimoto T, Kajimoto Y, Shirai Y, Murakami N, Nakai T, Komure O, Shirakawa O, Mita T, Nakai H (1993) Increase in [3H]cAMP binding sites and decrease in Gia and Goa immunoreactivities in left temporal cortices from patients with schizophrenia. Brain Res 615: 41–49

    Google Scholar 

  • Nukada T, Tanabe T, Takahashi H, Noda M, Haga K, Haga T, Ichiyama A, Kanagawa K, Hiranaga M, Matsuo H, Numa S (1986) Primary structure of the α-subunit of bovine adenylate cyclase-inhibiting G-protein deduced from the cDNA sequence. FEBS Lett 197: 305–310

    Google Scholar 

  • Okada F, Crow TJ, Roberts GW (1990) G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain. J Neural Transm [GenSect] 79: 227–234

    Google Scholar 

  • Okada F, Crow TJ, Roberts GW (1991) G-proteins (Gi, Go) in the medial temporal lobe in schizophrenia. Preliminary report of a neurochemical correlate of structural change. J Neural Transm [GenSect] 84: 147–153

    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 (1990) Schizophrenia: the cellular biology of a functional psychosis. Trends Neurosci 13: 207–211

    Google Scholar 

  • Schaffner W, Weissmann C (1973) A rapid, sensitive, and specific method for the determination of protein in dilute solution. Anal Biochem 56: 502–514

    Google Scholar 

  • Shelton RC, Weinberger DR (1986) X-ray computerized tomography studies of schizophrenia: a review and synthesis. In: Nasrallah HA, Weinberger DR (eds) The neurology of schizophrenia. Elsevier, Amsterdam, pp 207–250

    Google Scholar 

  • Strittmatter SM, Valenzuela D, Kennedy TE, Neer EJ, Fishman MC (1990) Go is a major growth cone protein subject to regulation by GAP-43. Nature 344: 836–841

    Google Scholar 

  • Suddath RL, Casanoca MF, Goldberg TE, Daniel DG, Kelsoe JR, Weinberger DR (1989) Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. Am J Psychiatry 146: 464–472

    Google Scholar 

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

    Google Scholar 

  • Sullivan KA, Liao Y-C, Alborzi A, Beiderman B, Chang F-H, Masters SB, Levinson AD, Bourne HR (1986) Inhibitory and stimulatory G-proteins of adenylate cyclase: cDNA and amino acid sequences of the α-chains. Proc Natl Acad Sci USA 83: 6687–6691

    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 

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Author notes

  1. F. Okada

    Present address: Health Administration Center, Hokkaido University, Sapporo, Japan

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    Y. Tokumitsu

  2. Hokkaido Institute of Technology, Sapporo, Japan

    N. Takahashi

  3. Division of Psychiatry, Clinical Research Centre, Harrow

    T. J. Crow

  4. Department of Anatomy and Cell Biology, St. Mary's Hospital Medical School, London, UK

    G. W. Roberts

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  1. F. Okada
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  2. Y. Tokumitsu
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  3. N. Takahashi
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  4. T. J. Crow
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  5. G. W. Roberts
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Okada, F., Tokumitsu, Y., Takahashi, N. et al. Reduced concentrations of the α-subunit of GTP-binding protein Go in schizophrenic brain. J. Neural Transmission 95, 95–104 (1994). https://doi.org/10.1007/BF01276428

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  • DOI: https://doi.org/10.1007/BF01276428

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