ADP Receptor P2Y12 Is Expressed in Vascular Smooth Muscle Cells and Stimulates Contraction in Human Blood Vessels.

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title = "ADP Receptor P2Y12 Is Expressed in Vascular Smooth Muscle Cells and Stimulates Contraction in Human Blood Vessels.",
abstract = "Objective - ADP plays an important role in platelet aggregation by activating P2Y(12) receptors. We assessed the hypothesis that P2Y(12) receptors are expressed in vascular smooth muscle cells (VSMC). Methods and Results - P2Y(12) receptor mRNA was found to have a high expression among the P2 receptors in human VSMC, significantly higher than the other 2 ADP receptors (P2Y(1) and P2Y(13), real-time polymerase chain reaction). Western blots gave a band of 50 kD, similar to that in platelets. To unmask a P2Y(12) receptor-mediated vasoconstriction by simulating the in vivo situation, vessels were precontracted to a submaximal level. 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small veins (E-max = 15 +/- 6% of 60 mmol/L K+ contraction, pEC(50) = 5.6 +/- 0.6, E-max = 21 +/- 1%, pEC(50) = 6.8 +/- 0.1, and E-max = 48 +/- 9%, pEC(50) = 6.6 +/- 0.4). The selective P2Y(12) antagonist AR-C67085 blocked 2-MeSADP contractions. The contraction was not reduced in patients using clopidogrel, a drug inhibiting ADP-induced platelet aggregation by blocking the P2Y(12) receptor. This may be explained by the high instability of the active clopidogrel metabolite that never reaches the systemic circulation. Conclusion - ADP acting on P2Y(12) receptors not only is important for platelet activation but also stimulates vasoconstriction. Stable drugs with antagonistic effects on P2Y(12) receptors, affecting both platelets and VSMC, could be of double therapeutic benefit in their prevention of both thrombosis and vasospasm.",
keywords = "vasoconstriction, platelets, ADP, P2Y receptors",
author = "Anna-Karin Wihlborg and Lingwei Wang and Braun, {Oscar Ostberg} and Atli Eyjolfsson and Ronny Gustafsson and Tomas Gudbjartsson and David Erlinge",
year = "2004",
doi = "10.1161/01.ATV.0000142376.30582.ed",
language = "English",
volume = "24",
pages = "1810--1815",
journal = "Arteriosclerosis, Thrombosis and Vascular Biology",
issn = "1524-4636",
publisher = "Lippincott Williams & Wilkins",
number = "10",