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.
Article PDF
Avoid common mistakes on your manuscript.
References
American Psychiatric Association (1987) Diagnostic and statistical manual, 3rd ed rev. APA Press, Washington DC
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
Birnbaumer L (1990) G proteins in signal transduction. Annu Rev Pharmacol Toxicol 1031: 163–224
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
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
Laemmli UK (1970) Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature 277: 680–685
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
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
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
Manji HK (1992) G proteins: implications for psychiatry. Am J Psychiatry 149: 746–760
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
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
Pfeuffer T (1977) GTP-binding protein in membranes and the control of adenylate cyclase activity. J Biol Chem 252: 7224–7234
Simon MI, Strathmann MP, Gautam N (1991) Diversity of G proteins in signal transduction. Science 252: 802–808
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
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
Wachtel H (1990) The second-messenger dysbalance hypothesis of affective disorders. Pharmacopsychiatry 23: 27–32
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
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244984