ISSN:
1369-1600
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1080/13556210500122995
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