Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-27T23:04:56.706Z Has data issue: false hasContentIssue false

Cyclic AMP Second-Messenger Signal Amplification in Depression

Published online by Cambridge University Press:  02 January 2018

Seth Kindler
Affiliation:
Jerusalem Mental Health Center, Ezrath Nashim Hospital

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.

Type
Research Article
Copyright
Copyright © Royal College of Psychiatrists, 1988 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III). Washington, DC: APA.Google Scholar
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.Google Scholar
Boyum, A. (1964) Separation of white blood cells. Nature, 204, 793794.Google Scholar
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.Google Scholar
Cheung, W. Y. (1967) Properties of cyclic 3′, 5′-nucleotide phosphodiesterase from rat brain. Biochemistry, 6, 10791087.Google Scholar
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.Google Scholar
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).Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle Scholar
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.Google Scholar
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.Google Scholar
Esler, M., Turbott, J. & Schwarz, J. (1982) The peripheral kinetics of norepinephrine in depressive illness. Archives of General Psychiatry, 39, 295300.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle Scholar
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology. Kensington, MD: George Washington University.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.