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A novel mechanism of vasoregulation: ADP‐induced relaxation of the porcine isolated coronary artery is mediated via adenosine release
Author(s) -
Rayment Sarah J.,
Ralevic Vera,
Barrett David A.,
Cordell Rebecca,
Alexander Stephen P. H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7050com
Subject(s) - adenosine , adenosine deaminase , chemistry , purinergic signalling , adenosine a1 receptor , adenosine a2b receptor , adenosine receptor , adenosine diphosphate , receptor , adenine nucleotide , purinergic receptor , adenosine a2a receptor , adenosine deaminase inhibitor , nucleoside , extracellular , p2 receptor , pharmacology , agonist , medicine , biochemistry , biology , nucleotide , platelet , platelet aggregation , gene
In this study, we have investigated the mechanism of ADP‐induced relaxation of porcine coronary artery (PCA) rings. The P2Y receptor agonists ADP and ADPβS produced concentration‐dependent relaxation of endothelium‐denuded PCA smooth muscle with p D 2 values of 5.3 and 4.9, respectively. RT‐polymerase chain reaction (RT‐PCR) and immunoblotting demonstrated mRNA and protein expression of P2Y 1 and A 2A adenosine receptors in the PCA. The nonselective P2 antagonist PPADS or the P2Y 1 ‐selective antagonist MRS2179 failed to alter ADP‐ or ADPβS‐induced relaxations. Relaxations to ADP were, however, blocked by the A 2A adenosine receptor‐selective antagonists ZM241385 and SCH58261 (apparent p K B values of 9.2 and 8.9, respectively). We excluded roles for direct occupancy of A 2A adenosine receptors by ADP or ADPβS as well as metabolism to adenosine as mechanisms for ADP‐evoked relaxations. However, ADP responses were significantly enhanced in the presence of the ENT1 nucleoside transporter inhibitors dipyridamole and NBTI and were significantly inhibited by adenosine deaminase, indicating a role for extracellular adenosine. Suprafusion of [ 3 H]‐adenine‐labeled PCA segments showed that ADP induced the release of a number of purines, including adenosine. These data suggest that ADP mediates relaxation of the PCA via a novel mechanism that involves adenine nucleotide‐evoked adenosine release and the subsequent activation of A 2A receptors.—Rayment, S. J., Ralevic, V., Barrett, D. A., Cordell, R. and Alexander, S. P. H. A novel mechanism of vasoregulation: ADP‐induced relaxation of the porcine isolated coronary artery is mediated via adenosine release FASEB J. 21, 577–585 (2007)