title: Modulation of the dinucleotide receptor present in rat midbrain synaptosomes by adenosine and ATP.
abstract: 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.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, E.U. Optica, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Díaz-Hernández
authors.forename: J
authors.initials: J
authors.lastname: Pintor
authors.forename: M T
authors.initials: MT
authors.lastname: Miras-Portugal
mesh_terms: 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
chemical_list: 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