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

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.

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.

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.

The actions of Ap₅A and ATP on the intrasynaptosomal Ca²⁺ increase did not cross‐desensitize.

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.

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.

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.

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.

DOI: 10.1111/j.1476-5381.1995.tb15894.x

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