Brain [3H]cAMP binding sites are unaltered in depressed suicides, but decreased by antidepressants.
Saturation binding of [3H]cAMP to the regulatory subunit of cAMP-dependent protein kinase (PKA) was measured in the soluble fraction of brain samples, obtained at post-mortem, from suicides with a firm retrospective diagnosis of depression and individually matched controls. Suicides were subdivided into those who had been free of antidepressant drugs for at least 3 months and those in whom prescription of antidepressants was clearly documented. In antidepressant-free suicides, we found no significant differences in the number or affinity of [3H]cAMP binding sites in the five regions studied. In antidepressant-treated suicides however, Bmax values were lower in all regions, reaching statistical significance in parietal cortex and amygdala. Kd values for antidepressant-treated suicides were significantly higher in parietal cortex, temporal cortex and amygdala. These results suggest the regulatory subunit of PKA is unaltered in depression, but is influenced by antidepressant drugs.
Lowther
S
S
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, UK. slowther@sghms.ac.uk
Katona
C L
CL
Crompton
M R
MR
Horton
R W
RW
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D011869:Radioligand Assay; D013405:Suicide; D014316:Tritium
D000928:Antidepressive Agents; D014316:Tritium; D000242:Cyclic AMP