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ABSTRACT
Endogenous nucleosides have multiple roles in human organism. Their synthetic analogues are used in the therapy of viral diseases and neoplasm, causing many adverse effects in various organs, including the heart. Intracellular localization is necessary for function of both endogenous and synthetic nucleosides. Therefore, we thought that it would be important to investigate the parameters (initial and total uptake), as well as the mechanism of transport of these substances across the cellular membrane of cardiac myocytes. The endogenous nucleosides we used were adenosine and thymidine. Tiazofurine was the synthetic purine analogue. We used single pass paired tracer dilution method in isolated and retrogradely perfused guinea pig heart.
Our results indicate that adenosine transport is saturable, depends on the presence of Na+ and uses a different transport system than its nucleic base, adenine. Similar results were obtained for the pyrimidine nucleoside thymidine. What was different was that its transport is significantly lower than that of adenosine and uses a different transport system. The transport of tiazofurine is saturable, can be inhibited by nucleoside transport inhibitors, and only partially uses the endogenous nucleosides transport system.
The results of this and the similar experiments provide us with the basis for comprehension of nucleoside analogues transport mechanism. This is important for estimation of their therapeutic benefit, as well as the possibility of diminishment of their adverse effects.
Keywords: adenosine, thymidine, tiazofurine, transport, heart
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