KMID : 0361519990100020150
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Korean Journal of Psychopharmacology 1999 Volume.10 No. 2 p.150 ~ p.157
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Effects of Selective Serotonin Reuptake Inhibitors(SSRIs) on Serotonin-mediated Intracellular Ca2£« Mobilization in Human Platelets
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Han Joon-Kyu
Park Ki-Chang Kim Hye-Kyung Lee Joong-Woo
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Abstract
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Objective£ºThe effects of treatment with selective serotonin reuptake inhibitors (SSRIs) on serotonin (5-HT)-mediated Ca2£« mobilization were investigated in the platelets of human healthy volunteers.
Method£ºThe serotonin (5-HT)-mediated Ca2£« mobilization in the platelets was assessed by the fluorescence technique with fura-2/AM.
Results£ºSSRIs (fluoxetine, paroxetine and sertraline) themselves mobilized intracellular Ca2£«([Ca2£«]i) in a dose-dependent fashion. The increment of [Ca2£«]i might be induced partly by the release from the intracellular calcium store, but mostly induced by the calcium transport through membrane. Stimulation of platelets with 10 ¥ìM 5-HT caused a rapid and sustained increase in [Ca2£«] i levels. Resting [Ca2£«] i before 5-HT treatment was 43.37¡¾1.25 nM. Fluoxetine inhibited the increment of [Ca2£«] i induced by 10 ¥ìM 5-HT with an IC50 value of 6.36 ¥ìM. Paroxetine augmented 5-HT-mediated increases in [Ca2£«] i, ranging from 117.76¡¾2.79% to 316.22¡¾18.39%, with an EC50 value of 19.68 ¥ìM. Sertraline also augmented 5-HT-mediated increases in [Ca2£«] i in a dose-dependent fashion, ranging from 106.29¡¾3.40% to 269.29¡¾14.96%, with an EC50 value of 11.40 ¥ìM.
Conclusions£ºIt is likely that SSRIs increase in intracellular free calcium level directly and show the inhibiting and augmenting effects on 5-HT-mediated Ca2£« movements. The precisemechanisms underlying the effects of 5-HT-mediated [Ca2£«] i response after treatment with SSRIs remain unclear£»however, the present finding suggests the possibility that a direct, or indirect, effect to intracellular Ca2£« signaling may be at least partly involved in the mechanism of action of SSRIs.
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KEYWORD
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SSRIs, Platelets, Intracellular Ca2£«, 5-HT
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