Mechanism of 3-deazaguanine transport in the rat heart

Abstract

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.