Premium
The stable pyrimidines UDPβS and UTPγS discriminate between the P2 receptors that mediate vascular contraction and relaxation of the rat mesenteric artery
Author(s) -
Malmsjö Malin,
Adner Mikael,
Harden T Kendall,
Pendergast William,
Edvinsson Lars,
Erlinge David
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703536
Subject(s) - p2y receptor , uridine triphosphate , agonist , uridine diphosphate , receptor , adenosine , medicine , p2 receptor , endocrinology , contraction (grammar) , purinergic receptor , adenosine triphosphate , chemistry , suramin , biology , nucleotide , biochemistry , gene , enzyme
The contractile and relaxant effects of the different P2 receptors were characterized in the rat isolated mesenteric artery by use of extracellular nucleotides, including the stable pyrimidines uridine 5′‐O‐thiodiphosphate (UDPβS) and uridine 5′‐O‐3‐thiotriphosphate (UTPγS). The selective P2X receptor agonist, αβ‐methylene‐adenosine triphosphate (αβ‐MeATP) stimulated a potent (pEC 50 =6.0) but relatively weak contraction ( E max =57% of 60 m M K + ). The contractile concentration‐response curve of adenosine triphosphate (ATP) was biphasic when added in single concentrations. The first part of the response could be desensitized by αβ‐MeATP, indicating involvement of P2X receptors, while the second part might be mediated by P2Y receptors. The contractile P2Y receptors were further characterized after P2X receptor desensitization with 10 μ M αβ‐MeATP. Uridine diphosphate (UDP), uridine triphosphate (UTP) and ATP stimulated contraction only in high concentrations (1–10 m M ). The selective P2Y 6 agonist, UDPβS, and the P2Y 2 /P2Y 4 ‐receptor agonists UTPγS and adenosine 5′‐O‐3‐thiotriphosphate (ATPγS) were considerably more potent and efficacious ( E max ∼250% of 60 m M K + ). Adenosine 5′‐O‐thiodiphosphate (ADPβS) was inactive, excluding contractile P2Y 1 receptors. After precontraction with 1 μ M noradrenaline, UTP, ADP and ATP induced relaxations with similar potencies (pEC 50 ∼5.0). UTPγS, ADPβS and ATPγS were approximately one log unit more potent indicating the presence of endothelial P2Y 1 and P2Y 2 /P2Y 4 receptors. The P2Y 6 receptor agonist, UDPβS, had no effect. UDPβS and UTPγS are useful tools when studying P2 receptors in tissue preparations with ectonucleotidase activity. Contractile responses can be elicited by stimulation of P2Y 6 and, slightly less potently, P2Y 2 /P2Y 4 receptors. The P2X response was relatively weak, and there was no P2Y 1 response. Stimulation of P2Y 1 and P2Y 2 /P2Y 4 receptors elicited relaxation, while P2Y 6 did not contribute.British Journal of Pharmacology (2000) 131 , 51–56; doi: 10.1038/sj.bjp.0703536