Effect of antidepressants on intracellular Ca++ mobilization in human frontal cortex.
BACKGROUND
It is well documented that central serotonin (5-HT)2 receptor dysfunction is involved in the biochemistry and pathophysiology of depression and might be corrected by antidepressant drug treatment.


METHODS
The effect of imipramine (IMI) and fluoxetine (FLX) on 5-HT2A receptor-mediated intracellular calcium ([Ca++]i) mobilization in synaptosomes of human frontal cortex was studied. [Ca++]i was measured using Fura-2AM.


RESULTS
It was observed that in response to 5-HT (10 mumol/L) there was a significant increase (254%; p < .001) in [Ca++]i compared to basal level (140.00 +/- 31.77 nmol/L/mg protein). Both IMI and FLX (10-1000 nmol/L) induce mobilization of basal [Ca++]i in a dose-dependent manner. IMI and FLX antagonize the 5-HT-stimulated [Ca++]i mobilization in a dose-dependent manner. IMI showed higher antagonizing effect at lower concentration (10 nmol/L); however, FLX showed maximum antagonizing effect at higher concentration (1000 nmol/L).


CONCLUSIONS
It is observed that imipramine and fluoxetine have different effects on antagonizing the 5-HT response in frontal cortex. One mode of action of these antidepressants might be by decreasing the intracellular calcium.
Jagadeesh
S R
SR
Neurochemistry Department, National Institute of Mental Health and Neurosciences, Bangalore, India.
Subhash
M N
MN
D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D002118:Calcium; D002121:Calcium Channel Blockers; D005473:Fluoxetine; D007099:Imipramine; D011500:Protein Synthesis Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors