DIADENOSINE POLYPHOSPHATES EVOKE CA2-PIG BRAIN VIA RECEPTORS DISTINCTFROM THOSE FOR ATP( TRANSIENTS IN GUINEA)

1. The ability of diadenosine polyphosphates, namely P-1,P-2-di(adenos ine) pyrophosphate (Ap2A), P-1,P-3-di(adenosine) triphosphate (Ap3A), P-1,P-4-di(adenosine) tetraphosphate (Ap4A), P-1,P-5-di(adenosine) pen taphosphate (Ap5A) and P-1,P-6-di(adenosine) hexaphosphate (Ap6A) to e voke Ca2+ signals in synaptosomes prepared from three different region s of the guinea-pig brain was examined. 2. In synaptosomal preparation s from the paleocortex (cortex), diencephalon/brainstem (midbrain) and cerebellum all the dinucleotides evoked Ca2+ signals that were concen tration dependent over the range 1-300 mu M. ATP and its synthetic ana logues, alpha,beta-methylene ATP, 2-methylthio ATP and adenosine 5'-O( 2-thio)diphosphate (all 100 mu M) also evoked Ca2+ signals in these pr eparations. 3. In the midbrain and cerebellum preparations, responses to ATP and its analogues were attenuated or abolished by the P2 recept or antagonist suramin (100 mu M) but responses to the dinucleotides we re not. Also, desensitization by a dinucleotide blocked responses to d inucleotides but not mononucleotides, and desensitization by a mononuc leotide blocked responses to mononucleotides but not dinucleotides. 4. In cortical preparations, suramin (100 mu M) blocked responses to bot h classes of nucleotides. Furthermore, there was mutual crass-desensit ization between the mono-and dinucleotides. 5. The adenosine A(1) rece ptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine, did not affect re sponses evoked by the dinucleotides, nor did the pyrimidine UTP. 6. It is concluded that there are specific dinucleotide receptors, activate d by diadenosine polyphosphates, but not ATP or UTP, on synaptic termi nals in guinea-pig diencephalon/brainstem and cerebellum. These recept ors bear a similarity to the dinucleotide receptor (P-4 receptor) in r at brain. In guinea-pig cerebral cortex synaptosomes, diadenosine poly phosphates appear to act via the same receptor as ATP.