Diadenosine polyphosphates evoke Ca2+ transients in guinea‐pig brain via receptors distinct from those for ATP

Abstract

1 The ability of diadenosine polyphosphates, namely P¹,P²‐di(adenosine) pyrophosphate (Ap2A), P¹,P³‐di(adenosine) triphosphate (Ap3A), P¹,P⁴‐di(adenosine) tetraphosphate (Ap4A), P¹,P⁵‐di(adenosine) pentaphosphate (Ap5A) and P¹,P⁶‐di(adenosine) hexaphosphate (Ap6A) to evoke Ca²⁺ signals in synaptosomes prepared from three different regions of the guinea‐pig brain was examined. 2 In synaptosomal preparations from the paleocortex (cortex), diencephalon/brainstem (midbrain) and cerebellum all the dinucleotides evoked Ca²⁺ signals that were concentration dependent over the range 1‐300 μm. ATP and its synthetic analogues,α,β‐methylene ATP, 2‐methylthio ATP and adenosine 5‘‐O‐(2‐thio)diphosphate (all 100 μm) also evoked Ca²⁺ signals in these preparations. 3 In the midbrain and cerebellum preparations, responses to ATP and its analogues were attenuated or abolished by the P2 receptor antagonist suramin (100μm) but responses to the dinucleotides were not. Also, desensitization by a dinucleotide blocked responses to dinucleotides but not mononucleotides, and desensitization by a mononucleotide blocked responses to mononucleotides but not dinucleotides. 4 In cortical preparations, suramin (100μm) blocked responses to both classes of nucleotides. Furthermore, there was mutual cross‐desensitization between the mono‐ and dinucleotides. 5 The adenosine A₁ receptor antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine, did not affect responses evoked by the dinucleotides, nor did the pyrimidine UTP. 6 It is concluded that there are specific dinucleotide receptors, activated by diadenosine polyphosphates, but not ATP or UTP, on synaptic terminals in guinea‐pig diencephalon/brainstem and cerebellum. These receptors bear a similarity to the dinucleotide receptor (P₄ receptor) in rat brain. In guinea‐pig cerebral cortex synaptosomes, diadenosine polyphosphates appear to act via the same receptor as ATP.