Lack of effect of antidepressants on mononuclear leukocyte G-protein levels or function in depressed outpatients.
Evidence from studies in animal and cultured cell models suggests that antidepressants (ADs) may enhance postreceptor signalling through the G protein coupled adenylyl cyclase (AC) pathways. To test whether this also occurs in patients receiving AD treatment, G-protein-activated-AC activity and the levels of alpha s and alpha i were measured in mononuclear leukocytes (MNLs) from 12 subjects with major depressive disorder (MDD) at baseline and after a 5 week trial of AD treatment. Although no differences were found in GTP gamma S-and forskolin-stimulated AC activity or the levels of alpha s and alpha i in MDD subjects compared with age- and sex-matched healthy subjects, pretreatment basal AC activity was significantly lower in treatment responders compared with healthy subjects. No significant changes were evident in any of these biochemical measures following 5 weeks of AD treatment in the patient group as a whole or stratified by response. These findings do not support an effect of ADs on the G-protein AC pathway, at least in MNLs. Lower pretreatment basal AC activity in responders suggests some change(s) in post-receptor signalling processes may be associated with an increased likelihood of therapeutic response to ADs.
Young
L T
LT
Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, Toronto, Canada.
Li
P P
PP
Kamble
A
A
Siu
K P
KP
Warsh
J J
JJ
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008297:Male; D015398:Signal Transduction / Q000187:drug effects
D000928:Antidepressive Agents; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases