CYP2B6 is expressed in African Green monkey brain and is induced by chronic nicotine treatment

Anna M. Lee, Sharon Miksys, Roberta Palmour, Rachel F. Tyndale

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

CYP2B6 is a drug-metabolizing enzyme expressed in human tissues that can activate bupropion (a smoking cessation drug) and tobacco smoke nitrosamines and can inactivate drugs such as nicotine. Smokers have higher brain CYP2B6 protein levels compared to non-smokers but the cause of this elevation is unknown. We investigated the basal expression and the effect of chronic nicotine treatment on CYP2B6 protein in African Green monkey (Cercopithecus aethiops) brain. Basal expression of brain CYP2B6 was strong in specific cells such as the frontal cortical pyramidal cells, the cerebellar Purkinje cells and the neurons in the substantia nigra. Basal CYP2B6 protein levels varied 2.7-fold (non-significant) among 12 brain regions. All monkeys were given a subcutaneous 0.1 mg/kg nicotine test dose prior to treatment and the maximum plasma concentration achieved was 87 ± 69 ng/ml and the half-life was 2.6 ± 1.5 h. Monkeys were treated subcutaneously twice daily with nicotine at 0.05 mg/kg for 2 days, 0.15 mg/kg for 2 days followed by 0.3 mg/kg for 18 days (n = 6) or saline (n = 6). Chronic nicotine treatment induced CYP2B6 expression in specific cells such as astrocytes and neurons in the frontal cortex, caudate, thalamus and hippocampus. CYP2B6 protein levels were induced 1.5-fold in the frontal cortex (p < 0.01). Hepatic CYP2B6 expression was not altered by nicotine. In conclusion, CYP2B6 protein is expressed in specific cells in monkey brain and is induced by chronic nicotine treatment which may impact central metabolism of CYP2B6 substrates such as bupropion and nicotine.

Original languageEnglish (US)
Pages (from-to)441-450
Number of pages10
JournalNeuropharmacology
Volume50
Issue number4
DOIs
StatePublished - Mar 1 2006

Fingerprint

Cercopithecus aethiops
Nicotine
Brain
Haplorhini
Bupropion
Purkinje Cells
Frontal Lobe
Proteins
Cytochrome P-450 CYP2B6
Pharmaceutical Preparations
Nitrosamines
Pyramidal Cells
Substantia Nigra
Smoking Cessation
Thalamus
Smoke
Astrocytes
Tobacco
Half-Life
Hippocampus

Keywords

  • Brain
  • Bupropion
  • CYP2B6
  • Induction
  • Monkey
  • Nicotine
  • Smoking

Cite this

CYP2B6 is expressed in African Green monkey brain and is induced by chronic nicotine treatment. / Lee, Anna M.; Miksys, Sharon; Palmour, Roberta; Tyndale, Rachel F.

In: Neuropharmacology, Vol. 50, No. 4, 01.03.2006, p. 441-450.

Research output: Contribution to journalArticle

Lee, Anna M. ; Miksys, Sharon ; Palmour, Roberta ; Tyndale, Rachel F. / CYP2B6 is expressed in African Green monkey brain and is induced by chronic nicotine treatment. In: Neuropharmacology. 2006 ; Vol. 50, No. 4. pp. 441-450.
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