Modulation of the dinucleotide receptor present in rat midbrain synaptosomes by adenosine and ATP

1 Diadenosine polyphosphates activate dinucleotide receptors in rat midbrain synaptic terminals. The agonist with highest affinity at this receptor, diadenosine pentaphosphate (Ap(5)A), elicits Ca2+ transients at concentrations ranging from 10(-7) to 10(-3) M with a single-phase curve and an EC50 value of 56.21+/-1.82 mu M. 2 Treatment of synaptosomal preparations with alkaline phosphatase (AP) changes the dose-response control curve into a biphasic one presenting two EC50 values of 6.47+/-1.25 nM and 11.16+/-0.83 mu M respectively. 3 The adenosine A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) reversed the biphasic concentration-response for Ap,A curve in the presence of AP, to a monophasic one with an EC50 value of 76.05+/-7.51 mu M. 4 The application of adenosine deaminase produced the same effect as DPCPX, the EC50 value for Ap,A, in the presence of AP being 18.62+/-4.03 mu M. 5 Activation of the adenosine A(1) receptor by means of cyclohexyladenosine (CHA) shifted the dose response curve for Ap,A to the left, resulting in a monophasic curve with an EC50 of 5.01+/-0.02 pM. 6 The destruction of extrasynaptosomal nucleotides by AP or the addition of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a broad P2 antagonist compound, enhance maximal effect of the Ap(5)A up to 55.6% on the dose response curve, thus suggesting a negative modulation by P2 receptors. 7 In a summary, ATP and adenosine present at the extra-synaptosomal space, an relevant natural modulators of the dinucleotide receptor, via P2 and adenosine A(1) receptors respectively.