JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by ORTON, T. C.
Right arrow Articles by FOUTS, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by ORTON, T. C.
Right arrow Articles by FOUTS, J. R.
Journal of Pharmacology And Experimental Therapeutics, Vol. 186, Issue 3, 482-497, 1973
Copyright © 1973 by American Society for Pharmacology and Experimental Therapeutics

XENOBIOTIC ACCUMULATION AND METABOLISM BY ISOLATED PERFUSED RABBIT LUNGS

T. C. ORTON 1, M. W. ANDERSON 1, R. D. PICKETT 1, T. E. ELING 1, and J. R. FOUTS 1

1 National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina

A study was made of the uptake and metabolism of various amines by isolated perfused rabbit lungs, artificially ventilated and perfused via the pulmonary artery with heparin-treated. autologous whole blood. Pulmonary hemodynamics remained constant and lung morphology was normal during 2 hours of perfusion. The basic amines (pKa > 8.5) were accumulated to a much greater extent than the nonbasic amines (pKa < 7.0). When added to the perfusion fluid in amounts of 0.2 to 100 µmol (2-1000 µM), chlorcyclizine. methadone, imipramine and amphetamine were highly accumulated (50-95% of a dose) by the lungs, whereas aniline, imidazole and propazine were poorly accumulated (10-20% of a dose). The uptake of all chemicals tested was rapid and a steady state was reached in 10 minutes. The quaternary ammonium compound paraquat was not accumulated by the lungs. but all concentrations used caused massive edema. The accumulation of the basic amines, chlorcyclizine, methadone, imipramine and amphetamine, involved a concentration-dependent uptake process, whereas the accumulation of the nonionized, neutral amines, aniline, imidazole and propazine, was nonsaturable and probably involved diffusion. None of the amines studied, except methadone, were apparently metabolized by the lungs during the 60 minutes of perfusion. The results indicate that rabbit lungs can be regarded as an important site of storage for basic amines and that the isolated perfused rabbit lung accumulated several basic chemicals and drugs that others have shown to localize or concentrate in lung tissue in vivo. The perfused rabbit lung may be useful in studying the mechanisms of such concentration of chemicals by the lung.

Submitted on March 2, 1973
Accepted on April 26, 1973




This article has been cited by other articles:


Home page
 Br J AnaesthHome page
F. Boer
Drug handling by the lungs
Br. J. Anaesth., July 1, 2003; 91(1): 50 - 60.
[Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
B. Moorthy, K. M. Parker, C. V. Smith, J. R. Bend, and S. E. Welty
Potentiation of Oxygen-Induced Lung Injury in Rats by the Mechanism-Based Cytochrome P-450 Inhibitor, 1-Aminobenzotriazole
J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 553 - 560.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics.