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

Publisher Website
Google Scholar
Abstract
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

This publication has 28 references indexed in Scilit: