Inhibitory effect of nicotine on benzo(a)pyrene elimination and marked pulmonary metabolism of nicotine in isolated perfused rat lung.
Concomitant administration of nicotine to the perfusion medium of an isolated perfused rat lung decreased the pulmonary elimination of benzo(a)pyrene entering the lung by vascular access. This inhibitory effect of nicotine was observed at a concentration of 0.5 microM nicotine in the perfusion medium. The elimination half-life of benzo(a)pyrene given as a bolus to establish an initial concentration of 1 microM in the perfusate was increased by a factor of about 3 after the addition of nicotine at 60 min of perfusion. A comparably high increase of the benzo(a)pyrene steady-state concentration was observed during constant infusion experiments when nicotine as the interfering substrate was infused parallelly after a control period of 60 min. In perfused rat lungs the rate of metabolism of nicotine given as a bolus (initial concentration of 0.5 microM) was comparable to the rate in isolated rat livers for 5,6-benzoflavone, oil or saline pretreated animals. Induction of cytochrome P-450 by pretreatment of the rats with phenobarbital caused an eightfold increase of the nicotine clearance in isolated livers, whereas the pulmonary nicotine clearance was almost doubled. Overall, expressed per g organ weight, the isolated perfused rat lung exhibited a marked capacity to metabolize nicotine while even the maximally induced phenobarbital-stimulated rat liver reached only 60% of the corresponding clearance values (per g organ) of the isolated rat lung. For the 5,6-benzoflavone and control treatments, values of 14%-21% were estimated for the liver compared with lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Foth
H
H
Abteilung für Pharmakologie und Toxikologie, Universität Göttingen.
Rüdell
U
U
Ritter
G
G
Kahl
G F
GF
D000818:Animals; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000493:pharmacokinetics / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D001564:Benzo(a)pyrene; D009538:Nicotine