Abstract
Background
Biochemical research on the etiopathogenesis of affective disorders has focused on
transduction mechanisms beyond receptors, such as adenylate cyclase activity.
Methods
Adenylate cyclase activity (AC) was measured in postmortem frontal cortex samples
from 11 suicide victims with a firm antemortem diagnosis of major depressive disorder
and 11 matched control cases. We analyzed the basal activity of the enzyme and that
following stimulation with forskolin, guanine nucleotides, and the β1-adrenoceptor agonist xamoterol.
Results
A significant negative correlation between the period of tissue storage and the response
of AC to the different stimuli assayed was observed. No difference was found in the
levels of basal, forskolin-, and GTPγS-stimulated activity between control and major
depressive disorder cases, both in the drug-free and the drug-treated subgroups. In
contrast, we found a significant lower response to β1-adrenoceptors agonist-stimulated AC activity in the major depressive disorder group
(p < .01). This pattern of reduced response was also found in the subgroup of patients
with negative toxicology for antidepressants.
Conclusions
These results, directly obtained from the brain of depressed patients, reinforce the
involvement of noradrenergic neurotransmission in depressive illness. They also support
the relevance of cyclic adenosine monophosphate signaling pathways in the etiopathogenesis
of affective disorders.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnostic and Statistical Manual of Mental Disorders.American Psychiatric Press, Washington, DC1987 (3rd ed., rev)
- Diagnostic and Statistical Manual of Mental Disorders.American Psychiatric Press, Washington, DC1996 (4th ed)
- Age-related changes in bindings of second messengers in the rat brain.Brain Res. 1995; 704: 227-232
- Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims.Arch Gen Psychiatry. 1990; 47: 1038-1047
- Regionally selective increases in β-adrenergic receptor density in the brains of suicide victims.Brain Res. 1988; 442: 199-203
- Chronic antidepressant treatment facilitates G protein activation of adenylyl cyclase without altering G protein content.J Pharmacol Exp Ther. 1995; 275: 509-517
- Adenylyl cyclase activity and G-protein subunit levels in post-mortem frontal cortex of suicide victims.Brain Res. 1994; 633: 297-304
- Brain β-adrenoceptor binding sites in depressed suicide victims.Psychopharmacology. 1991; 105: 283-288
- G Protein-coupled cyclic AMP signalling in postmortem brain of subjects with mood disorders.J Neurochem. 1999; 73: 1121-1126
- Changes in lymphocyte beta-adrenergic receptors in depression and mania.Psychiatry Res. 1979; 1: 191-197
- Dynamic regulation of leukocyte beta receptor-agonist interactions by physiological changes in circulating catecholamines.J Clin Invest. 1983; 72: 164-167
- Receptor-mediated activation of G proteins is increased in postmortem brains of bipolar affective disorder subjects.J Neurochem. 1996; 67: 1145-1152
- Up-regulation of immunolabeled alpha2A-adrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides.J Neurochem. 1999; 72: 282-291
- Alpha 2-adrenoceptor-mediated inhibition of platelet adenylyl cyclase and induction of aggregation in major depression. Effect of long–term cyclic antidepressant drug treatment.Arch Gen Psychiatry. 1990; 47: 125-132
- Neurotransmitter receptors in Alzheimer disease.Cerebrovasc Brain Metab Rev. 1993; 5: 61-94
- Blunted β-adrenergic responsivity of peripheral blood mononuclear cells in endogenous depression.Arch Gen Psychiatry. 1988; 45: 241-244
- Beta adrenergic receptor and cyclic AMP levels in intact human lymphocytes.Life Sci. 1984; 35: 855-863
- CNS signal transduction in the pathophysiology and pharmacotherapy of affective disorders and Schizophrenia.Synapse. 1993; 13: 278-293
- Decrease in epinephrine-induced attenuation of platelet adenylate cyclase activity in depressed patients.Neuropsychobiology. 1992; 26: 129-135
- Brain noradrenergic receptors in major depression and schizophrenia.Neuropsychopharmacology. 1999; 21: 69-81
- Evidence for a biochemical lesion in depression.J Clin Psychiatry. 2000; 61: 12-70
- GTP gamma S and forskolin-stimulated adenylyl cyclase activity in post-mortem brain from depressed suicides and controls.Mol Psychiatry. 1996; 1: 470-477
- Reduced sensitivity of lymphocyte beta-adrenergic receptors in patients with endogenous depression and psychomotor agitation.N Engl J Med. 1985; 313: 715-720
- A subsentivity of adenylyl cyclase coupled receptors on mononuclear leukocytes from drug-free inpatients with a major depressive episode.Biol Psychiatry. 1997; 42: 859-870
- Normalization of blunted lymphocyte β-adrenergic responsivity in melancholic inpatients by a course of electroconvulsive therapy.Arch Gen Psychiatry. 1990; 47: 461-464
- Increased serotonin2 and β-adrenergic receptor binding in the frontal cortices of suicide victims.Arch Gen Psychiatry. 1986; 43: 954-959
- Relation between lymphocyte beta-adrenergic responsivity and the severity of depressive disorders.Biol Psychiatry. 1994; 35: 920-925
- Forskolin-stimulated platelet adenylyl cyclase activity is lower in persons with major depression.Biol Psychiatry. 1997; 42: 30-38
- G proteins.in: Siegel G.J. Agranoff B.W. Albers R.W. Fisher S.K. Uhler M.D. Basic Neurochemistry. Molecular, Cellular and Medical Aspects. Lippincot-Raven, Philadelphia1999: 403-414
- Platelet adenylate cyclase activity in depression and after clomipramine and lithium treatment.Psychopharmacology. 1992; 109: 231-234
- The cardiovascular effects of ICI 118 587.Br J Pharmacol. 1982; 77: 381-388
- Imbalance in the Gs and Gi/o function in post-mortem human brain of depressed patients.J Neural Transm Gen Sect. 1993; 94: 63-69
- Alterations in phosphoinositide signalling and G-protein levels in depressed suicide brain.Brain Res. 1996; 723: 37-45
- Beta adrenergic receptor function in depression and the effect of antidepressant drugs.Acta Pharmacol Toxicol. 1985; 56: 66-79
- Neurotransmitter receptor mapping in human postmortem brain by autoradiography.in: Sharif N.A. Lewis M.E. Brain Imaging Techniques and Applications. Halsted Press, New York1989: 110-129
- Psychotherapeutic drugs and biogenic amines.Drugs. 1984; 28: 127-143
- Effects of freezing storage time on the density of muscarinic receptors in the human postmortem brain.Brain Res. 1996; 728: 65-71
- Recent studies on norepinephrine system in mood disorders.in: Bloom F.E. Meltzer H.Y. Psychopharmacology: The Four Generation of Progress. Raven Press, New York1995: 920-991
- Biometry.W.H. Freeman, New York1990
- Abnormalities in the cAMP signalling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium.Brain Res Bull. 2001; 55: 625-629
- β-adrenergic receptor binding in frontal cortex of suicide victims.Biol Psychiatry. 1991; 29: 183-191
- Existence of functional beta-1 and beta-2 adrenergic receptor on microglia.J Neurosci Res. 2002; 70: 232-237
- Dysbalance of neuronal second messenger function in the aetiology of affective disorders.J Neural Transm. 1989; 75: 21-29
- Cerebral cortex Gsα protein levels and forskolin-stimulated cyclic AMP formation are increased in bipolar affective disorders.J Neurochem. 1993; 61: 890-898
- Maturational, aging effects on guanine nucletide binding protein immunoreactivity in human brain.Dev Brain Res. 1991; 61: 243-248
Article info
Publication history
Accepted:
May 27,
2003
Received in revised form:
May 22,
2003
Received:
September 16,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
