Skip to main content Accessibility help
×
Home

Cyclic AMP Second-Messenger Signal Amplification in Depression

  • Richard P. Ebstein, Bernard Lerer, Baruch Shapira, Zecharia Shemesh, Daniel G. Moscovich and Seth Kindler (a1)...

Abstract

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

Copyright

Corresponding author

Jerusalem Mental Health Center, Ezrath Nashim Hospital, P.O.B. 140, Jerusalem, Israel

References

Hide All
American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III). Washington, DC: APA.
Barnes, R. F., Veith, R. C., Borson, S., Verhey, J., Raskind, M. A. & Halter, J. B. (1983) High levels of plasma catecholamines in dexamethasone-resistant depressed patients. American Journal of Psychiatry, 140, 16231625.
Boyum, A. (1964) Separation of white blood cells. Nature, 204, 793794.
Brown, B. L., Albano, J. D., Ekins, R. P., Scherzi, A. M. & Tampion, W. A. (1971) A simple and sensitive saturation assay method for the measurement of adenosine 3′, 5′-cyclic monophosphate. Biochemistry Journal, 121, 561562.
Cheung, W. Y. (1967) Properties of cyclic 3′, 5′-nucleotide phosphodiesterase from rat brain. Biochemistry, 6, 10791087.
Codina, J., Hildebrandt, J., Sunyer, T., Sekura, R. D., Manclark, C. R., Iyengar, R. & Birnbaumer, L. (1984) Mechanism in the vectorial receptor adenylate cyclase signal transduction. In Advances in Cyclic Nucleotide and Protein Phosphorylation Research (eds Greengard, P., Robison, G. A., Paoletti, R. & Nicosia, S.). New York: Raven Press.
Ebstein, R. P., Lerer, B., Bennett, E. R., Shapira, B., Kindler, S., Shemesh, Z. & Gerstenhaber, N. (1987b) Lithium modulation of second messenger signal amplification in man: inhibition of phosphatidylinositol-specific phospholipase C and adenylate cyclase activity. Psychiatry Research (in press).
Ebstein, R. P., Moscovich, D. G., Zeevi, S., Amiri, Z. & Lerer, B. (1987a) The effect of lithium in vitro and following chronic treatment on human platelet adenylate cyclase activity: post-receptor modification of second messenger signal amplification. Psychiatry Research, 21, 221238.
Ebstein, R. P., Oppenheim, G., Ebstein, B. S., Amiri, Z. & Stessman, J. (1986a) The cyclic AMP second messenger system in man: the effects of heredity, hormones, drugs, aluminium, age and disease on signal amplification. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 10, 323353.
Ebstein, R. P., Oppenheim, G., & Stessman, J. (1984) Alzheimer's disease: isoproterenol and prostaglandin El stimulated cyclic AMP accumulation in lymphocytes. Life Sciences, 34, 22392243.
Ebstein, R. P., Selinger, D., Mintzer, J., Oppenheim, G., Goldin, L. R., Ebstein, B. S., Brawman, O. & Shemesh, Z. (1986b) Hormone-stimulated adenylate cyclase activity in man: studies with peripheral models. In Alzheimer's and Parkinson's Diseases: Strategies for Research and Development (eds Fisher, A., Lachman, C. and Hanin, I.). New York: Plenum Press.
Ebstein, R. P., Steinitz, M., Mintzer, J., Lipshitz, I. & Stessman, J. (1985) Beta-adrenergic-stimulated adenylate cyclase activity in normal and EBV-transformed lymphocytes. Experientia, 41, 15521554.
Esler, M., Turbott, J. & Schwarz, J. (1982) The peripheral kinetics of norepinephrine in depressive illness. Archives of General Psychiatry, 39, 295300.
Extein, I., Tallman, J., Smith, C. C. & Goodwin, F. K. (1979) Changes in lymphocyte beta-adrenergic receptors in depression and mania. Psychiatry Research, 1, 191197.
Feldman, R. D., Limbird, L. E., Nadeau, J., Fitzgerald, G. A., Robertson, D. & Wood, A. J. J. (1983) Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines. Journal of Clinical Investigation, 72, 164170.
Fraser, J., Nadeau, J., Robertson, D. & Wood, A. J. J. (1981) Regulation of human leukocyte beta receptors by endogenous catecholamines: relationship of leukocyte beta receptor density to the cardiac sensitivity to isoproterenol. Journal of Clinical Investigation, 67, 17771784.
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology. Kensington, MD: George Washington University.
Lake, C. R., Pickar, D., Ziegler, M. G., Lipper, S., Slater, S. & Murphy, D. L. (1982) High plasma norepinephrine levels in patients with major affective disorders. American Journal of Psychiatry, 139, 13151318.
Mann, J. J., Brown, R. P., Halper, J. P., Sweeney, J. A., Kocsis, J. H., Stokes, P. E. & Bilezikian, J. P. (1985) Reduced sensitivity of lymphocyte beta-adrenergic receptors in patients with endogenous depression and psychomotor agitation. New England Journal of Medicine, 313, 715720.
Menkes, D. B., Rasenick, M. M., Wheeler, M. A. & Bitensky, M. W. (1983) Guanosinc triphosphate activation of brain adenylate cyclase: enhancement by long-term antidepressant treatment. Science, 219, 6567.
Mooney, J. J., Schatzberg, A. F., Cole, J. O., Kizuka, P. P. & Schildkraut, J. J. (1985) Enhanced signal transduction by adenylate cyclase in platelet membranes of patients showing antidepressant responses to alprazolam: preliminary data. Journal of Psychiatric Research, 19, 6575.
Newman, M. E., Solomon, H. & Lerer, B. (1986) Electroconvulsive shock and cyclic AMP signal transduction: effects distal to the receptor. Journal of Neurochemistry, 46, 16671669.
Oppenheimer, G., Mintzer, J., Halperin, Y., Eliakim, R., Stessman, J. & Ebstein, R. P. (1984) Acute desensitization of lymphocyte beta-adrenergic-stimulated adenylate cyclase in old age and Alzheimer's disease. Life Sciences, 35, 17951802.
Pandey, G. N., Dysken, M. W., Garner, D. L. & Davis, J. M. (1979) Beta-adrenergic receptor function in affective illness. American Journal of Psychiatry, 136, 675678.
Seamon, K. & Daly, J. W. (1981) Activation of adenylate cyclase by the diterpene forskolin does not require the guanine nucleotide regulatory protein. Journal of Biological Chemistry, 256, 97999801.
Stessman, J., Mintzer, J., Lipshitz, I., Shemesh, Z., Goldin, L. R. & Ebstein, R. P. (1985) Heritability of forskolin and hormone-stimulated adenylate cyclase activity in human lymphocytes. Journal of Cyclic Nucleotide and Protein Phosphorylation Research, 10, 317326.
Wright, A. F., Louden, J. B., Hampson, M. E., Crichton, D. N. & Steel, C. M. (1984) Beta-adrenoreceptor binding defects in lymphoblastoid cell lines from manic–depressive subjects. Clinical Neuropharmacology, 7, 194195.
Wyatt, R. J., Portnoy, B., Kupfer, D. J., Snyder, F. & Engelman, K. (1971) Resting plasma catecholamine concentrations in patients with depression and anxiety. Archives of General Psychiatry, 24, 6570.

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Cyclic AMP Second-Messenger Signal Amplification in Depression

  • Richard P. Ebstein, Bernard Lerer, Baruch Shapira, Zecharia Shemesh, Daniel G. Moscovich and Seth Kindler (a1)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *