کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5827381 1558926 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular and cellular pharmacologyClozapine and olanzapine inhibit proton currents in BV2 microglial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Molecular and cellular pharmacologyClozapine and olanzapine inhibit proton currents in BV2 microglial cells
چکیده انگلیسی

Excessive reactive oxygen species produced by NADPH oxidase in over-activated microglia can lead to neuronal death. Some atypical antipsychotic drugs possibly have anti-inflammatory properties and suppress the production of pro-inflammatory cytokines and reactive oxygen species from microglia. Voltage-gated proton channels (Hv1) are expressed in microglia and are required for NADPH oxidase-dependent reactive oxygen species generation, which could contribute to neuronal death and ischemic brain damage. In the present study, we examined the effects of the atypical antipsychotics clozapine, olanzapine and risperidone on proton currents in microglial BV2 cells. Clozapine and olanzapine inhibited proton currents with IC50 values of 9.8 μM and 84 μM, respectively. Risperidone, however, showed very weak inhibition of proton currents. Clozapine-induced inhibition of proton currents was not accompanied by a positive shift in the activation voltage or reversal potential, indicating that the inhibition was not mediated through an increase in the intracellular pH. Clozapine binds to a multitude of receptors, including serotonin, dopamine and muscarinic receptors. Serotonin receptors, however, were not responsible for the proton current inhibition by clozapine. Of the three drugs, only clozapine could reach concentrations to inhibit microglial proton currents in the brain at therapeutic doses. Thus, the anti-inflammatory activity of clozapine may be partly attributable to its inhibition of microglial proton currents.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 755, 15 May 2015, Pages 74-79
نویسندگان
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