TIAZOFURINE UPTAKE BY THE ISOLATED GUINEA-PIG HEART

Tiazofurine is a selective inhibitor of the enzyme inosine monophospha te dehydrogenase, and exhibits potent antitumor activity. Considering the potential side effects on the heart, [H-3] tiazofurine uptake into the cardiomyocytes, as well as the mechanism of transport, were studi ed in the isolated perfused guinea pig heart, using the rapid single c irculation, paired-tracer technique. The maximal cellular uptake (U-ma x) of [H-3] tiazofurine ranged from 19% to 25% of the injected dose, w ith total cellular uptake (U-tot) ranging 12.1-15.6%. The addition of unlabeled tiazofurine caused inhibition of [H-3] tiazofurine uptake, w ith a U-max value of 9.06 +/- 4.6%. Therefore, the uptake of tiazofuri ne into cardiomyocytes could be considered a saturable process. The in hibition of [H-3] tiazofurine uptake caused by adenosine and dipyridam ole was of the same degree as the inhibition by unlabeled tiazofurine. Thus, it can be assumed that nucleosides' transport system(s) are inv olved in transport of tiazofurine into myocardial cells.