Regional and cellular induction of nicotine-metabolizing CYP2B1 in rat brain by chronic nicotine treatment
Section snippets
Animals
Four groups (N = 6 per group) of adult male Wistar rats (250ā300 g; Charles River) were injected s.c., once per day, for 7 days with 0, 0.1, 0.3, or 1.0 mg nicotine base/kg body weight, in the form of nicotine bitartrate (Sigma) in sterile saline adjusted to pH 7.4. The doses used in this study provided a range that was both behaviorally and pharmacologically relevant. This range included doses at which rats develop nicotine tolerance (0.4 mg/kg over 12 days, continuous infusion, e.g. Ref. 25),
CYP2B in untreated rat brain
On immunoblots we found a single immunoreactive band in brain that comigrated with induced hepatic CYP2B1; this band was not detected when the antibody was preadsorbed with expressed rat CYP2B1 protein (inset, Fig. 1 A), providing evidence that we were measuring CYP2B1 in these studies [38]. Immunoreactive protein was detected in all brain regions examined (Fig. 1). The level of CYP2B1 was much lower than that found in rat liver (approximately 80-fold less than in untreated rat liver, and
Discussion
In this study we have shown that CYP2B1 protein and mRNA are expressed variably across rat brain regions and specific cell types. In addition, we demonstrated that nicotine, a CYP2B1 substrate, can induce CYP2B1 and, hence, its own metabolism. The induction occurred in rat brain, but not in rat liver, and the pattern of induction was brain region- and cell type-specific. The cell-type specific induction occurred both in cells that normally have detectable CYP2B1 and in those that either
Acknowledgements
We would like to thank Ms. Yvette Grybowski for her technical assistance. This work was funded by MRC Grant MT14173 and the Centre for Addictions and Mental Health.
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