Molecular physiology of platelet ADP receptors

Kunapuli, Satya P.

doi:10.1002/(sici)1098-2299(199811/12)45:3/4<135::aid-ddr8>3.0.co;2-b

Cited by 7 publications

(2 citation statements)

References 45 publications

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“…[1][2][3][4][5][6][7] We were interested to determine whether the P2Y 1 receptor was also the route by which ADP induces shape change in equine platelets.…”

Section: Introductionmentioning

confidence: 99%

Effects of P2Y 1 and P2Y 12 receptor antagonists on ADP-induced shape change of equine platelets: comparison with human platelets

2002

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Platelet activation by adenosine 5' -diphosphate (ADP) is via both P2Y(1 )and P2Y(12) receptors and leads to shape change and aggregation. The effects on ADP-induced platelet shape change of two P2Y(1) antagonists, adenosine 3'-phosphate, 5'-phosphosulfate (A3P5PS) and 2-deoxy-N(6)-methyladenosine 3', 5'-diphosphate (MRS-2179) and a P2Y(12) antagonist 2-propylthio-D-beta,gamma-dichloromethylene-adenosine 5'-triphosphate (AR-C67085MX) were determined by turbidimetric aggregometry and scanning electron microscopy (SEM) on equine and human platelets. The platelet aggregation was inhibited during aggregometry by 4-[4-[4(aminoiminomethyl)phenyl]-1-piperazinyl]-1-piperidin acid hydrochloride trihydrate (GR 144053F), an inhibitor of fibrinogen binding. From aggregation profiles, concentration-response curves and SEM we conclude that the shape change of equine platelets was susceptible to inhibition by the P2Y(1) antagonists A3P5PS and MRS-2179, but less so than human platelets. The P2Y(12) antagonist AR-C67085 did not influence significantly the shape change of either equine or human platelets.

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“…[1][2][3][4][5][6][7] We were interested to determine whether the P2Y 1 receptor was also the route by which ADP induces shape change in equine platelets.…”

Section: Introductionmentioning

confidence: 99%

Effects of P2Y 1 and P2Y 12 receptor antagonists on ADP-induced shape change of equine platelets: comparison with human platelets

2002

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“…Platelets possess at least two P2Y receptors whose combined action is required for full activation and aggregation in response to ADP [17][18][19][20][21][22][23] (Fig. 1).…”

Section: The Platelet P2y 1 and P2y 12 Receptors For Adp Intracellulamentioning

confidence: 99%

The Platelet ATP and ADP Receptors

Oury

Tóth-Zsámboki

Vermylen

et al. 2006

CPD

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Adenine nucleotides, ADP and ATP, are coreleased from dense granules during platelet activation, as well as from endothelial cells and damaged red blood cells following vascular injury. Through autocrine and paracrine mechanisms, these extracellular signaling molecules interact with the platelet P2 receptors to amplify ongoing platelet activation. Two receptors for ADP, the G q -protein-coupled P2Y 1 and G i -protein-coupled P2Y 12 and one receptor for ATP, the P2X 1 ion channel, have been identified on platelets. Due to distinct pharmacological properties and differential regulation, the P2Y and P2X receptors essentially operate on different scales of time and distance and trigger selective intracellular signaling cascades. Recent advances in the understanding of the P2Y receptor physiology have reinforced the concept of these receptors as useful targets for antithrombotic therapy. The function of P2X 1 in platelet activation only recently started to be unraveled. This review focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists, antagonists and inhibitors that allow their pharmacological discrimination.Key Words: Hemostasis, thrombosis, adenine nucleotides, P2Y 1 , P2Y 12 , P2X 1 , antithrombotic therapy. HISTORY AND CLASSIFICATION OF PURINERGIC RECEPTORSThe first report about the potent actions of an adenine compound, AMP, extracted from heart muscle, was published by Drury and Szent-Györgyi in 1929. Initial investigations focused on effects of adenosine and ATP on the heart and vasculature, or concerned the effects of purines on platelets [1] and on mast cells. Further insights into the physiological role of extracellular purines and pyrimidines were provided via the study of their biological sources [2]. In this respect, the detection of nucleotide release from the heart during hypoxia [3] or from skeletal muscle during contraction indicated that secretion of purine compounds might be coupled to metabolic demand to regulate local blood flow. ATP release from sensory nerves suggested that adenine nucleotides play a role as neurotransmitter or neuromodulator in the central and peripheral nervous system [4].These early publications established that purinergic nucleotides act as extracellular signaling molecules [5]. Nucleotides are now documented to contribute to a diverse range of physiological responses such as smooth muscle contraction, neurotransmission, exocrine and endocrine secretion, immune response, inflammation, platelet aggregation, male reproduction, nociception and modulation of cardiac function [6].Purines and pyrimidines mediate their effects by interacting with distinct cell-surface receptors. Purinergic receptors were first formally recognized by Burnstock in 1978 [7]. They were divided into two classes: at P1-purinoceptors adenosine is the principal natural ligand, while P2-purinoceptors recognize both purine and pyrimidine nucleotides Based on an increasin...

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Integrin αIIbβ3

Błędzka

Pesho

et al. 2013

Platelets

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Molecular physiology of platelet ADP receptors

Cited by 7 publications

References 45 publications

Effects of P2Y 1 and P2Y 12 receptor antagonists on ADP-induced shape change of equine platelets: comparison with human platelets

Effects of P2Y 1 and P2Y 12 receptor antagonists on ADP-induced shape change of equine platelets: comparison with human platelets

The Platelet ATP and ADP Receptors

Integrin αIIbβ3

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