P-glycoprotein does not actively transport nicotine and cotinine.
P-glycoprotein does not actively transport nicotine and cotinine.
复制标题
P-糖蛋白不主动转运尼古丁和可替宁。
DOI：
10.1080/13556210500122995
复制
发表时间：
2005
影响因子：
3.4
通讯作者：
Devane,CLindsay
中科院分区：
文献类型：
--
作者：
Wang,Jun-Sheng;Markowitz,JohnS;Donovan,JenniferL;Devane,CLindsay
The ABCB1 gene transporter P‐glycoprotein (P‐gp) exists in the blood – brain barrier (BBB) and placenta and limits many drugs passing through the BBB and placenta. Several recent studies have raised confounding results regarding the roles of P‐gp in nicotine disposition. To ascertain this question, we examined the effects of nicotine and its major oxidative metabolite, cotinine, on ATPase activity using P‐gp containing membranes, in which nicotine and cotinine‐stimulated inorganic P i was used as a marker of the binding affinity of nicotine and cotinine to P‐gp. At concentrations ranging from 5 to 1000 ?μm, both nicotine and cotinine produced modest stimulative effects on ATPase activity in the P‐gp containing membrane. The Clint values of nicotine and cotinine were 0.01 and 0.007 minute − 1 × 10 − 3, respectively. The positive control, verapamil, at concentrations ranging from 1 to 100?μ m, created apparent stimulative effects on ATPase activity, with a Clint value of 1.7 minute − 1 × 10 − 3, consistent with previously reported results. The results of the current study suggest that nicotine and cotinine were not actively transported by P‐gp out of the cells. The observed carrier‐mediated nicotine transport in various cell lines may be mediated by other transporter proteins but not P‐gp.
