Glutathione conjugation in the isolated perfused rabbit lung: the effects of carbon monoxide, buthionine sulfoximine and cibacron blue.
The effect of carbon monoxide (CO) on pulmonary glutathione-S-transferase (GST) activity was investigated using the isolated perfused rabbit lung (IPRL) preparation. CO at a concentration of 7.5% did not alter the conjugation of glutathione (GSH) with 1,2-epoxy-(p-nitrophenoxy)propane (ENP) in the IPRL. The rate of GSH conjugate formation with ENP was not altered when the lung was exposed to a selective inhibitor of gamma-glutamylcysteine synthetase, buthionine sulfoximine (0.1 mM), but was significantly diminished (P less than 0.01) by co-administration of GST inhibitor cibacron blue (1 microM) with ENP. These results indicate that the rabbit lung actively conjugates GSH with ENP and that this reaction may be decreased by specific inhibitors of GST. However, the rate of GSH conjugation is not affected by CO ventilation in the IPRL.
Yang
C M
CM
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Carlson
G P
GP
D000280:Administration, Inhalation; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology; D004852:Epoxy Compounds / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009596:Nitrophenols / Q000378:metabolism; D010477:Perfusion; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013379:Substrate Specificity; D014227:Triazines / Q000494:pharmacology
D000963:Antimetabolites; D004852:Epoxy Compounds; D007527:Isoenzymes; D009596:Nitrophenols; D011500:Protein Synthesis Inhibitors; D014227:Triazines; C064605:3-(4-nitrophenoxy)-2-(S-glutathionyl)-1-propanol; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C012842:Cibacron Blue F 3GA; C064606:1-(4-nitrophenoxy)-3-(S-glutathionyl)-2-propanol; D002248:Carbon Monoxide; C007606:1,2-epoxy-3-(p-nitrophenoxy)propane; D005982:Glutathione Transferase; D005978:Glutathione