Uptake of 3H-labeled 1-aminooxy-3-aminopropane by baby hamster kidney cells.
The uptake, catabolism, and release of H-labeled 1-aminooxy-3-aminopropane, a new putrescine analog shown to be a potent polyamine antimetabolite, into and from baby hamster kidney cells (BHK21/C13) were studied. The results show that [3H]-1-aminooxy-3-aminopropane (APA) is not concentrated in the cell, does not compete with polyamines for transport and reveals no difference in uptake between polyamine-depleted and control cells. After a 12-h culture, 60% of APA was recovered intact in the culture media. At this time point, only 30% of the intracellular radioactivity was intact APA, showing that the drug is catabolized in the cells. This intracellular ratio persisted throughout the 4-day culture period. The metabolites of APA were not characterized further. The results indicate that the drug is not recognized as a polyamine by the cells and does not replace or interfere with the polyamines in cellular functions. Thus, its potent affinity to ornithine decarboxylase and spermidine synthase is likely to be due to close structural similarity with the intermediates formed in these reactions. This has implications for the mechanisms involved.
Hyvönen
T
T
Department of Biochemistry, University of Kuopio, Finland.
Khomutov
A R
AR
Khomutov
R M
RM
Lapinjoki
S
S
Eloranta
T O
TO
D000818:Animals; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D000518:Eflornithine / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011437:Propylamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism
D065108:Ornithine Decarboxylase Inhibitors; D011437:Propylamines; C046252:1-aminooxy-3-aminopropane; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine