Induction of pulmonary cytochrome P4501A1: interactive effects of nicotine and mecamylamine.
The effect of the nicotinic receptor antagonist mecamylamine on nicotine-mediated convulsions and induction of pulmonary cytochrome P4501A1 (CYP1A1) was examined in the rat. Mecamylamine blocked the convulsions and inhibited CYP1A1 induction by nicotine at the level of CYP1A1 activity (93%) and protein (97%), but independently induced the enzyme also at the level of activity and protein. The results show that mecamylamine antagonizes both the CYP1A1 induction and convulsions by nicotine but, independently, is an inducer of the enzyme. The results indicate that CYP1A1 induction is not a consequence of the convulsant effects of nicotine.
Iba
M M
MM
Department of Pharmacology and Toxicology, Rutgers University, College of Pharmacy, EOHSI, Piscataway, NJ 08854, USA. iba@eohsi.rutgers.edu
Fung
J
J
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008464:Mecamylamine / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D019363:Cytochrome P-450 CYP1A1