Vasoconstrictor and vasodilator responses to various agonists in the rat perfused mesenteric arterial bed: selective inhibition by PPADS of contractions mediated via P2x‐purinoceptors

Abstract

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 μm). 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 μm) 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 μm PPADS. 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 10μm PPADS. In addition, acetylcholine‐and adenosine‐elicited relaxations were not influenced by 10 μm PPADS. The present results confirm the previously described selective P2x antagonism by PPADS, this compound being ineffective at muscarinic M3‐ and adenosine P1‐receptors as well as at α1‐adrenoceptors. There was some inhibition of P2y‐purinoceptors but at a much higher concentration than required for inhibition of P2x‐purinoceptors. In addition, this study provides evidence for the ineffectiveness of PPADS at both vasoconstriction‐and vasodilatation‐mediating P2u‐purinoceptors. 1994 British Pharmacological Society