Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets.
The serotonin uptake inhibitors sertraline, paroxetine and fluoxetine were compared with imipramine and the calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) and calmidazolium, for their effects on intracellular Ca2+ mobilization in human platelets. All serotonin uptake inhibitors and calmodulin antagonists augmented thrombin-mediated increases in intracellular Ca2+. Sertraline, calmidazolium and W-7 also caused large dose-dependent increases in baseline levels of intracellular Ca2+. There was a rough correlation between the ability to elevate intracellular Ca2+ and potencies for inhibition of calmodulin. Neomycin, an inhibitor of inositol trisphosphate (IP3) generation, significantly inhibited the effects of sertaline. This is consistent with a role of IP3 and calmodulin in the effects of these drugs.
Helmeste
D M
DM
Department of Psychiatry, Veterans Administration Medical Center, Long Beach, CA 90822, USA.
Tang
S W
SW
Reist
C
C
Vu
R
R
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D002478:Cells, Cultured; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D017374:Paroxetine / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline
D015057:1-Naphthylamine; D002118:Calcium; D002147:Calmodulin; D005473:Fluoxetine; D007099:Imipramine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline