Effects of Selective Serotonin Reuptake Inhibitors(SSRIs) on Serotonin-mediated Intracellular Ca2+ Mobilization in Human Platelets.
- Author:
Joon Kyu HAN
1
;
Ki Chang PARK
;
Hye Kyung KIM
;
Joong Woo LEE
Author Information
1. Department of Psychiatry, Physiology, Yonsei University, Wonju College of Medicine, Wonju, Korea. joonkyu@orgio.net
- Publication Type:Original Article
- Keywords:
SSRIs;
Platelets;
Intracellular Ca2+;
5-HT
- MeSH:
Calcium;
Fluorescence;
Fluoxetine;
Healthy Volunteers;
Humans*;
Inhibitory Concentration 50;
Membranes;
Paroxetine;
Serotonin Uptake Inhibitors;
Serotonin*;
Sertraline
- From:Korean Journal of Psychopharmacology
1999;10(2):150-157
- CountryRepublic of Korea
- Language:Korean
-
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.
