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Imbalance of the Gs and Gi/o function in post-mortem human brain of depressed patients

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Summary

The amounts of various G protein subunits in postmortem brain samples from the parietal and temporal cortices were the same in controls and depressive patients as demonstrated by immunoblotting. However, photoaffinity GTP labeling (AAGTP) of Gi/oα, but not Gsα, was significantly increased in depressives in both cortex regions. Furthermore, the ratio of Gs/Gi/o AAGTP incorporation revealed a significant reduction in depressives in these regions. The present findings suggest that an imbalance of second messengers via G protein function may be involved in the pathophysiology of depression.

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References

  • American Psychiatric Association (1987) Diagnostic and statistical manual, 3rd ed rev. APA Press, Washington DC

    Google Scholar 

  • Avissar S, Schreiber G (1992) The involvement of guanine nucleotide binding proteins in the pathogenesis and treatment of affective disorders. Biol Psychiatry 31: 435–459

    Google Scholar 

  • Birnbaumer L (1990) G proteins in signal transduction. Annu Rev Pharmacol Toxicol 1031: 163–224

    Google Scholar 

  • Gsell W, Lange KW, Pfeuffer R, Heckers S, Heinsen H, Senitz D, Jellinger K, Ransmayr G, Wichart I, Vock R, Beckmann H, Riederer P (1993) How to run a brain bank. A report from the Austro-German brain bank. J Neural Transm [Suppl] 39: 31–70

    Google Scholar 

  • Hatta S, Marcus MM, Rasenick MM (1986) Exchange of guanine nucleotide between GTP-binding proteins which regulate neuronal adenylate cyclase. Proc Natl Acad Sci USA 83: 5439–5443

    Google Scholar 

  • Laemmli UK (1970) Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature 277: 680–685

    Google Scholar 

  • Lesch KP, Manji HK (1992) Signal-transducing G proteins and antidepressant drugs: evidence for modulation of α-subunits gene expression in rat brain. Biol Psychiatry 32: 549–579

    Google Scholar 

  • Lesch KP, Aulakh CS, Tolliver TJ, Hill JL, Murphy DL (1991) Regulation of G proteins by chronic antidepressant drug treatment in rat brain: tricyclics but not clogyline increase Goα-subunits. Eur J Pharmacol-Mol Pharmacol 10 Sect 207: 361–364

    Google Scholar 

  • Li PP, Tam YK, Young LT, Warsh JJ (1991) Lithium decreases Gi-1, Gi-2 α-subunits mRNA levels in rat cortex. Eur J Pharmacol-Mol Pharmacol Sect 206: 165–166

    Google Scholar 

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

    Google Scholar 

  • Ozawa H, Rasenick MM (1989) Coupling of the stimulatory GTP-binding protein Gs to rat synaptic membrane adenylate cyclase is enhanced subsequent to chronic antidepressant treatment. Mol Pharmacol 36: 803–809

    Google Scholar 

  • Ozawa H, Rasenick MM (1991) Chronic electronconvulsive treatment augments coupling of the GTP-binding protein Gs to the catalytic moiety of adenylate cyclase in a manner similar that seen with chronic antidepressant drugs. J Neurochem 56: 330–338

    Google Scholar 

  • Pfeuffer T (1977) GTP-binding protein in membranes and the control of adenylate cyclase activity. J Biol Chem 252: 7224–7234

    Google Scholar 

  • Simon MI, Strathmann MP, Gautam N (1991) Diversity of G proteins in signal transduction. Science 252: 802–808

    Google Scholar 

  • Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of protein from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76: 4350–4354

    Google Scholar 

  • Wachtel H (1989) Dysbalance of neuronal second messenger function in aetiology of affective disorder; a pathophysiological concept hypothesizing defects beyond first messenger receptors. J Neural Transm 75: 21–29

    Google Scholar 

  • Wachtel H (1990) The second-messenger dysbalance hypothesis of affective disorders. Pharmacopsychiatry 23: 27–32

    Google Scholar 

  • Young LT, Li PP, Kish SJ, Siu KP, Warsh JJ (1991) Postmortem cerebral cortex Gsα-subunit levels are elevated in bipolar affective disorder. Brain Res 553: 323–326

    Google Scholar 

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Ozawa, H., Gsell, W., Frölich, L. et al. Imbalance of the Gs and Gi/o function in post-mortem human brain of depressed patients. J. Neural Transmission 94, 63–69 (1993). https://doi.org/10.1007/BF01244984

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  • DOI: https://doi.org/10.1007/BF01244984

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