Premium
Abstract no.: 7
Endothelium‐dependent relaxation evoked by ATP and UTP in the aorta of P2Y 2 ‐deficient mice
Author(s) -
Guns P.J. D.F.,
Van Assche T.,
Fransen P.,
Robaye B.,
Boeynaems J.M.,
Bult H.
Publication year - 2006
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2006.00420_7.x
Subject(s) - p2y receptor , purinergic receptor , receptor , uridine triphosphate , endocrinology , medicine , knockout mouse , calcium in biology , chemistry , agonist , nucleotide , biology , biochemistry , gene
Based on pharmacological criteria, we previously suggested that in the mouse aorta endothelium‐dependent relaxation by nucleotides is mediated by P2Y 1 (ADP), P2Y 2 (ATP) and P2Y 6 (UDP) receptors. For UTP it was unclear whether P2Y 2 , P2Y 6 or yet another subtype was involved. Therefore, in view of the lack of selective purinergic agonists and antagonists we used P2Y 2 ‐deficient mice to clarify the action of UTP. Thoracic aorta segments (width 2 mm) of P2Y 2 ‐deficient and wild type (WT) mice were mounted in organ baths to measure isometric force development and intracellular calcium signalling. Relaxations evoked by ADP, UDP and acetylcholine were identical in knockout and WT mice indicating that the receptors for these agonists function normally. P2Y 2 ‐deficient mice showed impaired ATP‐ and ATPγS‐evoked relaxation, suggesting that in WT mice ATP and ATPγS activate predominantly the P2Y 2 ‐subtype. The ATP/ATPγS‐evoked relaxation and calcium signals in the knockout mice were partially rescued by P2Y 1 , since they were sensitive to 2′‐deoxy‐N 6 ‐methyladenosine3′,5′‐bisphosphate (MRS2179), a P2Y 1 selective antagonist. In contrast to ATP, the UTP‐evoked relaxation was not different among knockout and WT mice. Moreover, the action of UTP was not sensitive to MRS2179. Therefore, the action of UTP is probably mediated mainly by a P2Y 6 (like) receptor subtype. In conclusion, we demonstrated that ATP‐evoked relaxation of the murine aorta is mainly mediated by P2Y 2 . But this P2Y 2 receptor has apparently no major role in UTP‐evoked relaxation. The vasodilator effect of UTP is probably mediated mainly by a P2Y 6 (like) receptor.