Summary
We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated.
This is a preview of subscription content, log in via an institution to check access.
References
Andrade R, Malenka RC, Nicoll RA (1986) A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 234: 1261–1265
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
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
Crow TJ (1987) The dopamine hypothesis survives, but there must be a way ahead. Br J Psychiatry 151: 460–465
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
De Vivo M, Maayani S (1986) Characterization of the 5-hydroxytryptamine1A receptormediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes. J Pharmacol Exp Ther 238: 248–253
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
Gilman AG (1984) G proteins and dual control of adenylate cyclase. Cell 36: 577–579
Graziano MP, Gilman AG (1987) Guanine nucleotide-binding regulatory proteins. Mediators of transmembrane signaling. Trends Pharmacol Sci 8: 478–481
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
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
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 Β γ-subunits in development of their biological activities. J Biol Chem 261: 8182–8191
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
Kerwin RW, Patel S, Meldrum BS, Czudek C, Reynolds GP (1988) Asymmetrical loss of a glutamate receptor subtype in left hippocampus in schizophrenia. Lancet i: 583–584
Kerwin RW (1989) How do the neuropathological changes of schizophrenia relate to preexisting neurotransmitter and aetiological hypotheses? Psychol Med 19: 563–567
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Milligan G, Gierschik P, Spiegel AM, Klee WA (1989) The GTP-binding regulatory proteins of neuroblastoma x glioma, NG 108-15, and glioma, C6 cells. Immunochemical evidence of a pertussis toxin substrate that is neither Ni nor No. FEBS Lett 195: 225–230
Okada F, Tokumitsu Y, Nomura Y (1989) Pertussis toxin attenuates 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes. J Neurochem 52: 1566–1569
Okada F, Crow TJ, Roberts GW (1990) G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain. J Neural Transm 79: 227–234
Reynolds GP (1983) Increased concentrations and lateral asymmetry of amygdala dopamine in schizophrenia. Nature 305: 527–529
Reynolds GP (1989) Beyond the dopamine hypothesis. The neurochemical pathology of schizophrenia. Br J Psychiatry 155: 315–316
Reynolds GP, Czudek C, Andrews HB (1990) Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia. Biol Psychiatry 27: 1038–1044
Roberts GW, Bruton CJ (1990) Notes from the graveyard. Schizophrenia and neuropathology. Neuropathol Appl Neurobiol 16: 1–16
Suki WN, Abramowitz J, Mettera R, Codina J, Birnbaumer L (1987) The human genome encodes at least three non-allellic G proteins with αi-type subunits. FEBS Lett 220: 187–192
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
VanDongen AMJ, Codina J, Olate J, Mattera R, Joho R, Birnbaumer L, Brown AM (1988) Newly identified brain potassium channels gated by the guanine nucleotide binding protein Go. Science 242: 1433–1437
Wing JK, Cooper JE, Sartorius N (1974) Measurement and classification of psychiatric symptoms. Cambridge University Press, London
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Okada, F., Crow, T.J. & Roberts, G.W. G proteins (Gi, Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change. J. Neural Transmission 84, 147–153 (1991). https://doi.org/10.1007/BF01249119
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01249119