The effects of no synthesis inhibition on the uptake of endogenous nucleosides into the rat brain

Brain uptake of H-3 endogenous nucleosides in rats was measured by Brain Uptake Index method, using C-14-sucrose as a referent molecule. The values obtained in control group were 4.68+/-0.93 for adenosine, 4.10+/-0.72 for guanosine and 1.14+/-0.72 for thymidine, indicating significant blood-to-brain transport of purine nucleosides. NO-synthase inhibition was induced by i.p. application of 25mg/kg 1-omega-nitro-arginin methyl ester (L-NAME) and 5mg/kg diphenylethiodonium (brain parenchyma NOS inhibitor). HPLC analysis showed that the concentration of L-NAME in brain was sufficient to cause inhibition of NOS. Application of L-NAME resulted in significant inhibition of brain uptake for both purine nucleosides. Unlike adenosine, in the case of guanosine a correlation between the rate of brain uptake inhibition and the L-NAME concentration in plasma, but not in brain, was obtained. Application of diphenylethiodonium also caused a significant decrease in both guanosine and adenosine brain uptake. The obtained results were not significantly different from the BUI values obtained after preapllication of L-NAME. Our results suggest that NOS inhibition decreases brain uptake of purine nucleosides. Such effect(s) are probably due to the inhibition of brain parenchyma NOS.