Effects of Selective Serotonin Reuptake Inhibitors(SSRIs) on Serotonin-mediated Intracellular Ca2+ Mobilization in Human Platelets

Han, Joon Kyu; Park, Ki Chang; Kim, Hye Kyung; Lee, Joong Woo

Abstract

OBJECTIVE
The effects of treatment with selective serotonin reuptake inhibitors (SSRIs) on serotonin (5-HT)-mediated Ca(2+) mobilization were investigated in the platelets of human healthy volunteers. METHOD: The serotonin (5-HT)-mediated Ca(2+) mobilization in the platelets was assessed by the fluorescence technique with fura-2/AM.
RESULTS
SSRIs (fluoxetine, paroxetine and sertraline) themselves mobilized intracellular Ca(2+)([Ca(2+)]i) in a dose-dependent fashion. The increment of [Ca(2+)]i, might be induced partly by the release from the intracellular rat[ism store, but mostly induced by the calcium transport through membrane. Stimulation of platelets with 10 micrometer 5-HT caused a rapid and sustained increase in [Ca(2+)]i levels. Resting [Ca(2+)]i, before 5-HT treatment was 43.37+/-1.25 nM. Fluoxetine inhibited the increment of [Ca2+]i induced by 10 micrometer5-HT with an IC50 value of 6.36 micrometer. Paroxetine augmented 5-HT-mediated increases in [Ca2+]i, ranging from 117.76+/-2.79% to 316.22+/-8.39%, with an EC50 value of 19.68 micrometer. Sertraline also augmented 5-HT-mediated increases in [Ca(2+)]i in a dose-dependent fashion, ranging from 106.29+/-.40% to 269.29+/-4.96%, with an EC50it value of 11.40 micrometer.
CONCLUSIONS
It is likely that SSRIs increase in intracellular free calcium level directly and show the inhibiting and augmenting effects on 5-HT-mediated Ca(2+) movements. The precise mechanisms underlying the effects of 5-HT-mediated[Ca(2+)]i response after treatment with SSRIs remain unclear however, the present finding suggests the possibility that a direct, or indirect, effort to intracellular Ca(2+) signaling may be at least partly involved in the mechanism of action of SSRIs.