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Vasoconstrictor and vasodilator responses to various agonists in the rat perfused mesenteric arterial bed: selective inhibition by PPADS of contractions mediated via P 2x ‐purinoceptors
Author(s) -
Windscheif Ursula,
Ralevic Vera,
Bäumert Hans G.,
Mutschler Ernst,
Lambrecht Günter,
Burnstock Geoffrey
Publication year - 1994
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 - 10.1111/j.1476-5381.1994.tb17094.x
Subject(s) - ppads , vasodilation , mesenteric arteries , medicine , eledoisin , chemistry , endocrinology , pharmacology , purinergic receptor , adenosine , artery , neuropeptide , receptor , substance p
1 The effect of pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) on vasoconstrictor and/or vasodilator responses to various agonists and electrical field stimulation was investigated in the rat mesenteric arterial bed at basal tone and at tone raised by methoxamine (15–50 μ m ). 2 At basal tone, nucleotides produced vasoconstriction with the following rank order of potency: α,β‐methylene ATP > > 2‐methylthio ATP ≥ ATP = UTP. PPADS (0.3–10 μ m ) concentration‐dependently antagonized α,β‐methylene ATP‐, 2‐methylthio ATP‐ and ATP‐induced responses. UTP‐, noradrenaline‐ and nerve‐mediated (4–32 Hz) increases in perfusion pressure remained unaffected by 10 μ m PPADS. 3 In raised tone preparations, nucleotides produced vasodilations, their rank order of potency being 2‐methylthio ATP > ATP > UTP. Responses to 2‐methylthio ATP were slightly antagonized, whereas ATP‐ and UTP‐induced responses remained unaffected by 10μ m PPADS. In addition, acetylcholine‐and adenosine‐elicited relaxations were not influenced by 10 μ m PPADS. 4 The present results confirm the previously described selective P 2x antagonism by PPADS, this compound being ineffective at muscarinic M 3 ‐ and adenosine P 1 ‐receptors as well as at α 1 ‐adrenoceptors. There was some inhibition of P 2y ‐purinoceptors but at a much higher concentration than required for inhibition of P 2x ‐purinoceptors. 5 In addition, this study provides evidence for the ineffectiveness of PPADS at both vasoconstriction‐and vasodilatation‐mediating P 2u ‐purinoceptors.