Modulation of the dinucleotide receptor present in rat midbrain synaptosomes by adenosine and ATP.
Diadenosine polyphosphates activate dinucleotide receptors in rat midbrain synaptic terminals. The agonist with highest affinity at this receptor, diadenosine pentaphosphate (Ap(5)A), elicits Ca(2+) transients at concentrations ranging from 10(-7) to 10(-3) M with a single-phase curve and an EC(50) value of 56.21+/-1.82 microM. Treatment of synaptosomal preparations with alkaline phosphatase (AP) changes the dose-response control curve into a biphasic one presenting two EC(50) values of 6.47+/-1.25 nM and 11.16+/-0.83 microM respectively. The adenosine A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) reversed the biphasic concentration-response for Ap(5)A curve in the presence of AP, to a monophasic one with an EC(50) value of 76.05+/-7.51 microM. The application of adenosine deaminase produced the same effect as DPCPX, the EC(50) value for Ap(5)A, in the presence of AP being 18.62+/-4.03 microM. Activation of the adenosine A(1) receptor by means of cyclohexyladenosine (CHA) shifted the dose response curve for Ap(5)A to the left, resulting in a monophasic curve with an EC(50) of 5. 01+/-0.02 pM. 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. In a summary, ATP and adenosine present at the extra-synaptosomal space, are relevant natural modulators of the dinucleotide receptor, via P2 and adenosine A(1) receptors respectively.
Díaz-Hernández
M
M
Departamento de Bioquímica, Facultad de Veterinaria, E.U. Optica, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Pintor
J
J
Miras-Portugal
M T
MT
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
D015226:Dinucleoside Phosphates; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014662:Vasoconstrictor Agents; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase; D000241:Adenosine; D002118:Calcium