title: 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.
authors.affiliation: Institute of Physiology, School of Medicine, Visegradska 26, 11000 Belgrade, Serbia. mp011cz@gmail.com
authors.forename: M M
authors.initials: MM
authors.lastname: Petrovic
authors.forename: D
authors.initials: D
authors.lastname: Dekanski
authors.forename: A
authors.initials: A
authors.lastname: Isakovic
authors.forename: L
authors.initials: L
authors.lastname: Scepanovic
authors.forename: D M
authors.initials: DM
authors.lastname: Mitrovic
mesh_terms: D000225:Adenine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D033703:Nucleoside Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D051381:Rats; D012964:Sodium / Q000502:physiology; D013936:Thymidine / Q000494:pharmacology; D013941:Thymine / Q000494:pharmacology; D014316:Tritium
chemical_list: D004140:Dinitrophenols; D033703:Nucleoside Transport Proteins; D014316:Tritium; D006147:Guanine; C010567:3-deazaguanine; D012964:Sodium; D000225:Adenine; D000241:Adenosine; D013941:Thymine; D013936:Thymidine