A novel receptor for diadenosine polyphosphates coupled to calcium increase in rat midbrain synaptosomes

Open Access
Publisher Website
Google Scholar
Abstract
1 Diadenosine polyphosphates, AP4A and Ap5A, as well as ATP, α,β-MeATP and ADP-β-S, were able to elicit variable intrasynaptosomal Ca2+ increases in rat midbrain synaptic terminals. The origin of the Ca2+ increment was the extrasynaptosomal space since the elimination of extracellular Ca2+ abolished the effect of all the agonists. 2 The P2-purinoceptor antagonist, suramin, did not affect the Ca2+–increase evoked by diadenosine polyphosphates but dramatically blocked the Ca2+ entry induced by ATP and its synthetic analogues. 3 The actions of Ap5A and ATP on the intrasynaptosomal Ca2+ increase did not cross-desensitize. 4 Concentration-response studies for diadenosine polyphosphates showed pD2 values of 54.5 ±4.2 μm and 55.6 ±3.8 μm for AP4A and Ap5A, respectively. 5 The entry of calcium induced by diadenosine polyphosphates could be separated into two components. The first represented a selective voltage-independent Ca2+ entry; the second, a sustained phase which was voltage-dependent. 6 Studies on the voltage-dependent Ca2+–channels involved in the effects of the diadenosine polyphosphates, demonstrated that Ω-conotoxin G-VI-A inhibited the sustained Ca2+–entry, suggesting the participation of an N-type Ca2+–channel. This toxin was unable to abolish the initial cation entry induced by AP4A or Ap5A. Ω-Agatoxin IV-A, tetrodotoxin, or nifedipine did not inhibit the effects of the diadenosine polyphosphates. 7 The effect of ATP on Ca2+–entry was abolished by nifedipine and Ω-conotoxin G-VI-A, suggesting the participation of L- and N-type Ca2+–channels in the response to ATP. 8 These data suggest that AP4A, Ap5A and ATP activate the same intracellular Ca2+ signal through different receptors and different mechanisms. AP4A and Ap5A induce a more selective Ca2+–entry in a voltage-independent process. This is the first time that a selective action of diadenosine polyphosphate through receptors other than P1 and P2-purinoceptors has been described.