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Tiazofurine uptake by the isolated guinea pig heart.

Tiazofurine is a selective inhibitor of the enzyme inosine monophosphate dehydrogenase, and exhibits potent antitumor activity. Considering the potential side effects on the heart, [3H] tiazofurine uptake into the cardiomyocytes, as well as the mechanism of transport, were studied in the isolated perfused guinea pig heart, using the rapid single circulation, paired-tracer technique. The maximal cellular uptake (Umax) of [3H] tiazofurine ranged from 19% to 25% of the injected dose, with total cellular uptake (Utot) ranging 12.1-15.6%. The addition of unlabeled tiazofurine caused inhibition of [3H] tiazofurine uptake, with a Umax value of 9.06 +/- 4.6%. Therefore, the uptake of tiazofurine into cardiomyocytes could be considered a saturable process. The inhibition of [3H] tiazofurine uptake caused by adenosine and dipyridamole was of the same degree as the inhibition by unlabeled tiazofurine. Thus, it can be assumed that nucleosides' transport system(s) are involved in transport of tiazofurine into myocardial cells.