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P‐glycoprotein does not actively transport nicotine and cotinine
Author(s) -
Wang JunSheng,
Markowitz John,
Donovan Jennifer,
Devane C Lindsay
Publication year - 2005
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1080/13556210500122995
Subject(s) - cotinine , nicotine , chemistry , pharmacology , transporter , metabolite , alkaloid , verapamil , medicine , endocrinology , biochemistry , stereochemistry , gene , calcium
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.