Mechanism and Effect of Tumor Necrosis Factor a on Expression of P-glycoprotein and Absorption of RisperidoneChinese Full Text
XU Li-ping1,XIE Yong-biao2*,ZHOU Zhi-ling2(1.Guangzhou Psychiatric Hospital,Guangzhou 510370,China;2.Guangdong General Hospital∥Guangdong Academy of Medical Sciences,Guangdong Mental Health Institute,Guangzhou 510080,China)
Abstract: 【Objective】To explore the effect and mechanism of tumor necrosis factor a(TNF-a) on the P-glycoprotein(P-gp) expression and the absorption of risperidone in brain capillary endothelium cells.【Methods】Mouse brain capillary endothelium cell line bEnd.3 was incubated with TNF-a,and then JNK phosphorylation was detected by western blot.After the cells were pre-treated with SP600125 for 1 h(DMSO as vehicle control) and added with TNF-a,P-gp expression was analyzed by Western blot.Finally,bEnd.3 cells were incubated with TNF-a for 24 h and then added with risperidone for another 24 h,the concentration of risperidone in medium supernatant was assayed by HPLC-MS.【Results】 TNF-a increased JNK phosphorylation in bEnd.3 cells.TNF-a enhanced the P-gp expression,which was inhibited by SP600125.And TNF-a increased the concentration of risperidone in medium supernatant in bEnd.3 cells(μg/L,1.17 ± 0.18 vs 0.86 ± 0.17,P = 0.010).【Conclusion】 JNK pathway is involved in the process of TNF-a enhancing P-gp expression.TNF-a can decrease the absorption of risperidone in brain capillary endothelium cells.
- DOI:
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2011.0015
- Series:
- Subject:
- Classification Code:
R741
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