Add time:07/26/2019         Source:sciencedirect.com

The aim of this study was to see whether the compound adenosine 5′-tetraphosphate (Ap4) is active in the central nervous system by examining its effect on isolated rat brain synaptic terminals. Ap4 proved to be more resistant to ecto-enzymatic hydrolysis than adenosine triphosphate (ATP), showing only 2% hydrolysis after a 2-min incubation, compared to 75% for ATP.In addition, Ap4 was able to produce concentration-dependent increases in intracellular Ca2+ when applied extracellularly. This action was dependent upon the presence of extracellular calcium. Ap4 acts through ionotropic ATP receptors (P2X receptors) and not through diadenosine polyphosphate receptors, since ATP abolished the response elicited by Ap4 whereas Ap5A did not. Ap4, ATP and ATP-γ-S were of similar potency (EC50≈20 μM) while 2MeSATP, α,β-meATP and ADP-β-S possessed slightly lower potency (EC50≈50 μM).The P2-purinoceptor antagonists suramin and PPADS blocked the Ap4 effect. The IC50 values for these compounds were 35.5 and 7.8 μM respectively. Diinosine polyphosphates and inosine tetraphosphate inhibited the response elicited by Ap4 with IC50 values that varied between approximately 40 and 50 μM.These results show that Ap4 is as good an agonist as ATP on synaptosomal P2X receptors, being more resistant to extracellular hydrolysis by ecto-nucleotidases.

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