Independent blood-brain barrier transport systems for nucleic acid precursors.
The blood-brain barrier permeability to certain 14-C-labelled purine and pyrimidine compounds was studied by simultaneous injection in conjunction with two reference isotopes into the rat common carotid artery and decapitation 15s later. The amount of 14-C-labelled base or nucleoside remaining in brain was expressed in relation to 3-H2O (a highly diffusible internal standard) and 113m-In-labelled EDTA (an essentially non-diffusible internal standard). Of the 17 compounds tested, measurable, saturable uptakes were established for adenine, adenosine, guanosine, inosine and uridine. Two independent transport systems in the rat blood-brain barrier were defined. One transported adenine (Km equals 0.027 mM) and could be inhibited with hypoxanthine. Adenosine (Km equals 0.018 mM), guanosine, inosine and uridine all cross-inhibit, defining a second independent nucleoside carrier system. Adenosine inhibited [14-D]uridine uptake more effectively than did uridine, suggesting a weaker affinity of uridine for this nucleoside carrier.
D000225:Adenine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D006151:Guanosine / Q000378:metabolism; D007042:Hypoxanthines / Q000494:pharmacology; D007288:Inosine / Q000378:metabolism; D007700:Kinetics; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis*; D051381:Rats; D014529:Uridine / Q000378:metabolism
D007042:Hypoxanthines; D011687:Purines; D011743:Pyrimidines; D006151:Guanosine; D007288:Inosine; D012313:RNA; D004247:DNA; D000225:Adenine; D000241:Adenosine; D014529:Uridine