Wang Rong, Sun Xuan, Deng Yong-Shu, Qiu Xu-Wen
1 Nursing Department, Renmin Hospital of Wuhan University , Wuhan, China .
2 Department of Cardiology, Renmin Hospital of Songzi City , Songzi, China .
DNA Cell Biol. 2018 Apr;37(4):325-329. doi: 10.1089/dna.2017.4096. Epub 2018 Feb 14.
The alterations in P-glycoprotein (P-gp)-mediated transport of antipsychotics due to the ABCB1 1199G>A polymorphism were assessed in the current study. The ABCB1 and ABCB1 recombinant cell models were constructed to study the sensitivity, intracellular accumulation, and transepithelial permeability of antipsychotic drugs. ABCB1 recombinant cells had more sensitivity to olanzapine (2.2-fold, p < 0.01), aripiprazole (1.8-fold, p < 0.01), amisulpride (2.3-fold, p < 0.01), and risperidone (3.1-fold, p < 0.01) than ABCB1 cells, while the resistance to paliperidone in both recombinant cell models was similar. In addition, the uptake quality of olanzapine, aripiprazole, amisulpride, and risperidone in ABCB1 recombinant cells was greatly decreased compared to ABCB1 cells (3.2-fold, p < 0.01; 3.7-fold, p < 0.01; 3.1-fold, p < 0.01; 2.6-fold, and p < 0.01, respectively). Furthermore, apparent permeability values were greatly increased in ABCB1 recombinant cells compared with ABCB1 recombinant cells for olanzapine (2.7-fold, p < 0.01), aripiprazole (2.9-fold, p < 0.01), amisulpride (3.4-fold, p < 0.01), and risperidone (4.1-fold, p < 0.01). The influence of ABCB1 1199G>A polymorphism on the transport of P-gp-mediated substrates showed up as drug-specific. Collectively, the ABCB1 1199G>A polymorphism may impact effective antipsychotics concentration in target cells via mediating the agents transport and distribution.
在本研究中，评估了ABCB1 1199G>A多态性导致的P-糖蛋白（P-gp）介导的抗精神病药物转运改变。构建了ABCB1和ABCB1重组细胞模型，以研究抗精神病药物的敏感性、细胞内蓄积和跨上皮通透性。与ABCB1细胞相比，ABCB1重组细胞对奥氮平（2.2倍，p<0.01）、阿立哌唑（1.8倍，p<0.01）、氨磺必利（2.3倍，p<0.01）和利培酮（3.1倍，p<0.01）更敏感，而两种重组细胞模型对帕利哌酮的耐药性相似。此外，与ABCB1细胞相比，ABCB1重组细胞中奥氮平、阿立哌唑、氨磺必利和利培酮的摄取量大幅降低（分别为3.2倍，p<0.01；3.7倍，p<0.01；3.1倍，p<0.01；2.6倍，p<0.01）。此外，与ABCB1重组细胞相比，ABCB1重组细胞中奥氮平（2.7倍，p<0.01）、阿立哌唑（2.9倍，p<0.01）、氨磺必利（3.4倍，p<0.01）和利培酮（4.1倍，p<0.01）的表观通透性值大幅增加。ABCB1 1199G>A多态性对P-gp介导的底物转运的影响表现为药物特异性。总体而言，ABCB1 1199G>A多态性可能通过介导药物转运和分布影响靶细胞中有效抗精神病药物的浓度。
