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Uridine adenosine tetraphosphate (Up4A) as a novel coronary vasodilator in health and disease: Role of purinergic P1 and P2 receptors
Author(s) -
Zhou Zhichao,
Duncker Dirk Jan,
Merkus Daphne
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1055.5
Subject(s) - ppads , vasodilation , purinergic receptor , medicine , antagonist , adenosine , ionotropic effect , endocrinology , dilator , adenosine a2a receptor , vasoconstriction , coronary vasodilator , pharmacology , p2y receptor , receptor , chemistry , adenosine receptor , agonist , glutamate receptor
Up4A is a potent endothelium‐derived contracting factor that contains purine and pyrimidine moieties and activates purinergic P2X and P2Y receptors. Up4A has recently been found to also have vasodilator effects. Here, we evaluated Up4A in isolated coronary small arteries from normal (N) swine and swine after myocardial infarction (MI), and studied the purinergic receptor subtypes involved. Surprisingly, Up4A (10 −9 –10 −5 M) failed to induce contraction in small arteries from N and MI, but produced dose‐dependent relaxation in vessels from N and MI preconstricted with U46619. Sensitivity to Up4A was lower in MI than N. In N, Up4A induced vasodilation was reduced by nitric oxide (NO) inhibition with L‐NAME to a similar extent as by nonselective P1 antagonist 8PT and A2A antagonist SCH58261 , while nonselective P2 antagonist PPADS, P2X1 antagonist MRS2159, and P2Y1 antagonist MRS2179 had no effect. In MI, dilation by Up4A was blunted by P2‐ (PPADS, MRS2159, MRS2179) and P1‐inhibition (8PT, SCH58261 ) and L‐NAME. Q‐PCR confirmed the presence of coronary P2X1, P2Y1 and A2A receptors. Thus, Up4A exerts a dilator rather than a constrictor effect in coronary microvessels which in N occurs via P1 (particularly A2A) mediated activation of NO, and both P1 and P2 in MI. These findings indicate that the mechanism of vasodilation by Up4A is different in the diseased heart. Supported by China Scholarship Council (2009624027)