Adenylate cyclase activity in postmortem brain of suicide subjects: reduced response to beta-adrenergic stimulation.
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 beta(1)-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 GTPgammaS-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 beta(1)-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.
Valdizán
Elsa M
EM
Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain.
Gutierrez
Olga
O
Pazos
Angel
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D016022:Case-Control Studies; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D011869:Radioligand Assay / Q000379:methods; D013405:Suicide; D017307:Xamoterol / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D006150:Guanine Nucleotides; D005576:Colforsin; D017307:Xamoterol; D000262:Adenylyl Cyclases