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Characterization of P 2X ‐ and P 2Y ‐purinoceptors in the rabbit hepatic arterial vasculature
Author(s) -
Ralevic V.,
Mathie R.T.,
Alexander B.,
Burnstock G.
Publication year - 1991
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.1476-5381.1991.tb12308.x
Subject(s) - vasodilation , adenosine , purinergic receptor , sodium nitroprusside , medicine , methylene blue , endocrinology , adenosine triphosphate , chemistry , vasoconstriction , endothelium derived relaxing factor , pharmacology , biology , biochemistry , nitric oxide , photocatalysis , catalysis
1 Responses to adenosine 5′‐triphosphate (ATP) and its agonists were studied in the isolated liver of the rabbit dually perfused through the hepatic artery and the portal vein. 2 In the hepatic arterial vascular bed at basal tone, ATP and its agonists elicited vasoconstrictor responses with the rank order of potency α,β‐methylene ATP > 2‐methylthio ATP > ATP, consistent with their action at the P 2X ‐purinoceptor. 3 When tone was raised with noradrenaline (10 −5 m ), vasodilator responses were produced with ATP and 2‐methylthio ATP; α,β‐methylene ATP produced only further constriction. The rank order of vasodilator potency was 2‐methylthio ATP > ATP ≫ α,β‐methylene ATP, consistent with their action at the P 2Y ‐purinoceptor. 4 Methylene blue (10 −5 m ) antagonized vasodilator responses to acetylcholine and ATP, but not those to adenosine or sodium nitroprusside. Addition of 8‐phenyltheophylline (10 −5 m ) antagonized responses to adenosine but not those to sodium nitroprusside. Responses to ATP remaining after antagonism with methylene blue were not further antagonized by 8‐phenyltheophylline. 5 These results present evidence for discrete P 2X ‐ and P 2Y ‐purinoceptors in the rabbit hepatic arterial bed which mediate vasoconstrictor and vasodilator responses respectively. 6 Vasodilatation produced by ATP was entirely due to direct action at the P 2Y ‐purinoceptor, and not at a P 1 ‐purinoceptor following breakdown to adenosine. The antagonism of these responses by methylene blue is consistent with the view that vasodilatation by ATP takes place largely via endothelial P 2Y ‐purinoceptors that lead to release of endothelium‐derived relaxing factor. However, we cannot exclude the possibility that P 2Y ‐purinoceptors located on the vascular smooth muscle play a contributory role in ATP‐induced vasodilatation.