Receptor binding properties of di (1,N 6-ethenoadenosine) 5′, 5′′′-P 1, P 4-tetraphosphate and its modulatory effect on extracellular glutamate levels in rat striatum

Abstract

Our aim was to investigate the neuromodulatory role of diadenosine tetraphosphate (Ap 4A). Ap 4A-binding sites were detected in striatum and hippocampus membranes using [ 35S]-ADPβS as radioligand and Ap 4A and ε-(Ap 4A), di-ethenoadenosine tetraphosphate, as displacers. Effects of ε-(Ap 4A) on extracellular glutamate levels were studied using intracerebral perfusion. Both areas contain high-affinity binding sites for [ 35S]-ADPβS with K d values in the low nM range. [ 35S]-ADPβS binding was displaced by Ap 4A and ε-(Ap 4A). At 1 and 10 μM doses, ε-(Ap 4A) markedly decreased glutamate levels in the striatum. The possibility of Ap 4A acting as an endogenous modulator of excitatory neurotransmission is discussed.