The accumulation of cystamine and its metabolism to taurine in rat lung slices.
The objective of these studies was to determine the accumulation and fate of the disulphide, cystamine by rat lung slices. Cystamine was accumulated by two active uptake systems that obeyed saturation kinetics, with apparent Km values of 12 and 503 microM, and maximal rates of 530 and 5900 nmol/g wet weight/hr respectively. The high affinity system was competitively inhibited by the diamine, putrescine and the herbicide paraquat, which are themselves accumulated. Thus, this pulmonary uptake process appears to be identical for all three compounds. In contrast, the low affinity process was not inhibited by putrescine, and this process results from the diffusion of cystamine into the cell and its subsequent metabolism. Upon accumulation, cystamine was metabolised, predominantly to the sulphonic acid, taurine, with 10-20% of the intracellular label covalently binding to protein. Conversion to taurine was unaffected by amine oxidase inhibitors, but was decreased after GSH depletion, suggesting that pulmonary cystamine metabolism is glutathione-dependent, and is not mediated by diamine oxidase. Both cystamine and taurine have been implicated as antioxidants, and we suggest that cystamine is actively accumulated by the lung as part of the process to protect pulmonary tissue against oxidative stress.
Lewis
C P
CP
Biochemical Toxicology Section, Imperial Chemical Industries, PLC, Macclesfield, Cheshire, U.K.
Haschek
W M
WM
Wyatt
I
I
Cohen
G M
GM
Smith
L L
LL
D000818:Animals; D003538:Cystamine / Q000378:metabolism* / Q000493:pharmacokinetics; D003543:Cysteamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D010269:Paraquat / Q000493:pharmacokinetics; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000378:metabolism*
D013654:Taurine; D003543:Cysteamine; D005978:Glutathione; D010269:Paraquat; D003538:Cystamine; D011700:Putrescine