Diadenosine polyphosphates facilitate the evoked release of acetylcholine from rat hippocampal nerve terminals

Diadenosine polyphosphates are present in synaptic vesicles, are released u pon nerve stimulation and possess membrane receptors, namely in presynaptic terminals. However, the role of diadenosine polyphosphates to control neur otransmitter release in the CNS is not known We now show that diadenosine p entaphosphate (Ap(5)A, 3-100 muM) facilitated in a concentration dependent manner the evoked release of acetylcholine from hippocampal nerve terminals , with a maximal facilitatory effect of 116% obtained with 30 muM Ap(5)A. T he selective diadenosine polyphosphate receptor antagonist, diinosine penta phosphate (Ip(5)I, 1 muM), inhibited by 75% the facilitatory effect of Ap(5 )A (30 muM), whereas the P-2 receptor antagonists, suramin (100 muM) and py ridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 muM) only ca used a 18-24% inhibition, the adenosine A(1) receptor antagonist, 1,3-dipro pyl-8-cyclopentylxanthine (20 nM), caused a 36% inhibition and the adenosin e A(2A) receptor antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo [2,3- a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 20 nM), was devoid of e ffect. These results show that diadenosine polyphosphates act as neuromodul ators in the CNS, facilitating the evoked release of acetylcholine mainly t hrough activation of diadenosine polyphosphate receptors. (C) 2000 Elsevier Science B.V. All rights reserved.