Possible Existence of a Novel Receptor for Uridine Analogues in the Central Nervous System Using Two Isomers, N³-(S)-(+)- and N³-(R)-(−)-α-Hydroxy-β-phenethyluridines

抄録

Uridine analogue binding sites, the so-called uridine receptor, were observed in the experiments on specific [³H]N³-phenacyluridine binding to bovine synaptic membranes using two isomers, N³-(S)-(+)- and N³-(R)-(−)-α-hydroxy-β-phenethyluridine, as ligands. The potent hypnotic, N³-(S)-(+)-α-hydroxy-β-phenethyluridine, but not the (R)-isomer, strongly inhibited [³H]N³-phenacyluridine binding. The racemate had inhibitory activity intermediate between that of the two α-hydroxy-β-phenethyluridines ((R)- or (S)-isomers). The inhibitory constants of these compounds were determined. The K_i values of N³-phenacyluridine, α-hydroxy-β-phenethyluridine (racemate), N³-(R)-(−)-, and N³-(S)-(+)-α-hydroxy-β-phenethyluridine were 0.65, 397.4, 1908, and 10.2 nM, respectively. The present results indicate the existence of uridine receptors in the central nervous system in relation to their hypnotic activities reported previously.