Browsing by Author "Isakovic, A. (57202555421)"

The aim of this study was to determine the mechanism of transport of 3-deazaguanine in the rat heart. We used single-pass, paired-tracer dilution method on isolated and retrogradely perfused rat hearts. The maximal cellular uptake (Umax) and total cellular uptake (Utot) of 3-deazaguanine were determined under control conditions and under influence of possible modifiers. Both Umax and Utot were significantly reduced in the presence of unlabeled 3-deazaguanine (from 19.57±2.02% to 8.14±1.19% and from 16.49±3.65% to 4.70±1.96%, n=6, respectively). The presence of pyrimidine nucleoside thymidine caused the reduction of both Umax and Utot (from 20.03±3.76% to 13.58±3.16% and from 16.43±3.58% to 11.94±3.13%, n=6, respectively). Also, we tested the effect of the absence of sodium ions in perfusion solution (both Umax and Utot significantly reduced from 17.95±2.73% to 16.67±2.16% and from 16.68±2.97% to 14.81±3.04%, n=6, respectively) and the effect of dinitrophenol (both Umax and Utot significantly reduced from 19.09±3.68% to 10.58±3.14% and from 16.86±3.84% to 7.10±3.11%, n=6, respectively). The results of self- and cross-inhibition studies show that the transport of 3-deazaguanine is saturable, energy- and sodium-dependent and that 3-deazaguanine uses endogenous transport systems for thymidine and adenosine for its own transport. © 2006 Akadémiai Kiadó, Budapest.

Tiazofurin (TZF- beta-D-ribofuranosyl thiazole-4-carboxamide, NSC- 286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [ 3 H]-tiazofurin was determined in relation to the recovery of [ 14 C]- mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 ± 0.84% and was shown to be both carrier- mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 ± 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a K(m) 7.71 ± 1.42 μM, a V(max) of 1.30 ± 0.05 μM/min/g and a negligible constant of a free diffusion (K(2)) which suggests that the CP/CSF route may act as an alternative pathway into the brain. (C) 2000 Prous Science.

Tiazofurin (TZF- beta-D-ribofuranosyl thiazole-4-carboxamide, NSC- 286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [ 3 H]-tiazofurin was determined in relation to the recovery of [ 14 C]- mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 ± 0.84% and was shown to be both carrier- mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 ± 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a K(m) 7.71 ± 1.42 μM, a V(max) of 1.30 ± 0.05 μM/min/g and a negligible constant of a free diffusion (K(2)) which suggests that the CP/CSF route may act as an alternative pathway into the brain. (C) 2000 Prous Science.