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

• Published in: British journal of pharmacology 2000-05, Vol.130 (2), p.434-440
• Main Authors: Díaz‐Hernández, Miguel, Pintor, Jesús, Miras‐Portugal, M Teresa
• Format: Article
• Language: English
• Subjects: adenosine; Adenosine - metabolism; adenosine receptor; Adenosine Triphosphate - metabolism; alkaline phosphatase; Alkaline Phosphatase - metabolism; Animals; ATP; Calcium - metabolism; diadenosine polyphosphates; Dinucleoside Phosphates - metabolism; Dinucleoside Phosphates - pharmacology; dinucleotide receptor; Mesencephalon - drug effects; Mesencephalon - metabolism; Rats; Receptors, Purinergic P1 - metabolism; Receptors, Purinergic P2 - metabolism; Synaptosomes - drug effects; Synaptosomes - metabolism; Vasoconstrictor Agents - metabolism; Vasoconstrictor Agents - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703300

Diadenosine polyphosphates activate dinucleotide receptors in rat midbrain synaptic terminals. The agonist with highest affinity at this receptor, diadenosine pentaphosphate (Ap5A), 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 μM. 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 μM respectively. The adenosine A1 antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) reversed the biphasic concentration‐response for Ap5A curve in the presence of AP, to a monophasic one with an EC50 value of 76.05±7.51 μM. The application of adenosine deaminase produced the same effect as DPCPX, the EC50 value for Ap5A, in the presence of AP being 18.62±4.03 μM. Activation of the adenosine A1 receptor by means of cyclohexyladenosine (CHA) shifted the dose response curve for Ap5A to the left, resulting in a monophasic curve with an EC50 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 Ap5A 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 A1 receptors respectively. British Journal of Pharmacology (2000) 130, 434–440; doi:10.1038/sj.bjp.0703300