Adenylyl cyclase activity and G-protein subunit levels in postmortem frontal cortex of suicide victims

Basal and stimulated adenylyl cyclase activities and G s and G i protein α-subunit levels (G sα and G iα) were compared in postmortem frontal cortex from 18 suicide cases and 22 matched controls. Basal, guanosine 5′-O-(3-thiotriphosphate) (GTPγS) stimulated and forskolin stimulated enzyme activities were significantly lower in the suicide cases, compared to controls. These effects were most apparent in those suicides that had died from violent means or that had had a history of depression and appeared to reflect the lowered basal activity rather than a reduced ability of either GTPγS or forskolin to activate the enzyme. No significant correlations were found between adenylyl cyclase activity and either subject age or postmortem delay. Western blotting revealed no significant differences in G sα and G iα levels between control and suicide cases. However, levels of the smaller G sα isoform (G sα-S) showed a tendency to be increased in the violent death suicide and depressed suicide subgroups, compared to controls. Levels of the larger G sα isoform (G sα-L) showed a significant positive correlation with subject age. G iα levels showed a significant negative correlation with subject age and a positive correlation with postmortem delay. These results support the hypothesis that suicidal behaviour and depressive illness may be associated with an altered regulation of adenylyl cyclase.