Factors responsible for ADP-induced release reaction of human platelets

Mustard, J. F.; Perry, DW; Kinlough-Rathbone, R L; Packham, MA

doi:10.1152/ajplegacy.1975.228.6.1757

Cited by 340 publications

(150 citation statements)

References 0 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Results have been highly consistent except for tl%e well-known variation among donors for biphasic aggregation (9); from a single sample of platelet-rich plasma, biphasic aggregation is fully reproducible, but the concentration of stimulus required for biphasic aggregation is slightly different for each sample of platelet-rich plasma. Although biphasic aggregation may be an in vitro artifact (10), it is believed to reflect important physiological functions and is especially important as the only in vitro parameter of platelet function that is dependent upon prostaglandin synthesis. We have also observed some variation between donors in the rate of response of platelets to ADP; the traces selected for Fig.…”

Section: Methodsmentioning

confidence: 99%

Interrelations of Platelet Aggregation and Secretion

Charo¹,

Feinman²,

Detwiler³

1977

J. Clin. Invest.

338

117

View full text Add to dashboard Cite

A B S T R A C T The mechanism of stimulus-response coupling in human platelets was investigated with a new instrument that simultaneously monitors aggregation and secretion in the same sample of plateletrich plasma. When platelets were stimulated by high concentrations of ADP, secretion began only after aggregation was almost complete. With lower concentrations of ADP or with epinephrine, biphasic aggregation was observed, and secretion began simultaneously with, or slightly after, the second phase of aggregation. When platelets were stimulated with high concentrations of y-thrombin or A23187, secretion and aggregation began essentially together. With very low concentrations of y-thrombin or A23187, biphasic aggregation was observed with secretion paralleling the second phase. At every concentration of collagen, secretion and aggregation appeared to be parallel events. Under every condition where the beginning of secretion lagged behind aggregation, secretion was dependent upon aggregation and was inhibited by indomethacin; this is referred to as aggregation-mediated platelet activation. When secretion began at the same time as aggregation, it also occurred in the absence of aggregation and was not blocked by indomethacin; this is referred to as directly induced platelet activation. These observations are -consistent with a simple model of platelet stimulusresponse coupling that includes two mechanisms for activation; aggregation-mediated activation is inhibited by indomethacin, while direct activation does not depend upon aggregation and is not inhibited by indomethacin. Secretion and second wave aggregation appear to be parallel events, with little evidence for second wave aggregation being a consequence of secretion as usually described.

show abstract

Section: Methodsmentioning

confidence: 99%

Interrelations of Platelet Aggregation and Secretion

Charo¹,

Feinman²,

Detwiler³

1977

J. Clin. Invest.

338

117

View full text Add to dashboard Cite

show abstract

“…For instance, Gum et al defined aspirin resistance as a mean aggregation of Ն70% with 10 mol/L ADP and Ն20% with 0.5 mg/mL arachidonic acid. 42,43 Although aggregationdependent TxA 2 production can potentiate ADP-induced platelet aggregation in citrated PRP, 44,45 ADP, at 10 mol/L, induces full platelet aggregation that is largely independent of TxA 2 production. It is only at the intermediate concentrations of Ϸ2 to 4 mol/L that TxA 2 production causes amplification of the aggregation response to ADP (Figure 2).…”

Section: Failure Of Aspirin To Inhibit Platelet Function In Vivo or Imentioning

confidence: 99%

Aspirin and Clopidogrel

Cattaneo

2004

ATVB

370

133

View full text Add to dashboard Cite

Abstract-Aspirin and the thienopyridines ticlopidine and clopidogrel are antiplatelet agents that display good antithrombotic activity. In the past few years, the concept of aspirin resistance has been largely emphasized in the medical literature, although its definition is still uncertain. I suggest that "aspirin-resistant" should be considered as a description for those individuals in whom aspirin fails to inhibit thromboxane A 2 production, irrespective of the results of unspecific tests of platelet function, such as the bleeding time, platelet aggregation, or the PFA-100 system. Less well known than aspirin resistance, but certainly better characterized, is the issue of "clopidogrel resistance," which is probably mostly caused by inefficient metabolism of the prodrug clopidogrel to its active metabolite. At present, aspirin and clopidogrel resistance should not be looked for in the clinical setting, because there is no definite demonstration of an association with clinical events conditioning cost-effective changes in patient management. Key Words: aspirin resistance Ⅲ clopidogrel resistance Ⅲ antiplatelet agents Ⅲ cardiovascular diseases Ⅲ cerebrovascular diseases A spirin and the thienopyridines ticlopidine and clopidogrel are inhibitors of platelet aggregation that display good antithrombotic activity. They are used in the prophylaxis of patients undergoing vascular grafting or percutaneous angioplasty, in the medical management of acute coronary syndromes, and in long-term prevention of cardiovascular and cerebrovascular events.Both aspirin and the thienopyridines selectively inhibit a single pathway of platelet activation: aspirin affects the arachidonate-thromboxane A 2 (TxA 2 ) pathway by irreversibly inhibiting cyclo-oxygenase-1 (COX-1) (Figure 1). 1 The thienopyridines affect the adenosine diphosphate (ADP) pathway, by irreversibly blocking the ADP receptor P2Y 12 ( Figure 1). 2 Despite their selective mechanism of action, which does not counteract the many alternative pathways for platelet activation, aspirin and thienopyridines display a good antithrombotic activity. This is explained by the fact that both the arachidonate-TxA 2 pathway and the ADP pathway contribute to the amplification of platelet activation and are essential for the full aggregation and secretion response of platelets to agonists. 2

show abstract

“…Addition of ADP to washed platelets results in shape change, reversible aggregation at physiological concentrations of calcium (2 mM) and finally desensitization [10,11]. Transduction of the ADP signal involves a transient rise in free cytoplasmic calcium, due to mobilization of internal stores, secondary store-mediated influx and a concomitant inhibition of adenylyl cyclase activity [12].…”

Section: Introductionmentioning

confidence: 99%

P2 receptors and platelet function

Hechler

Gachet

2011

Purinergic Signalling

136

127

View full text Add to dashboard Cite

Following vessel wall injury, platelets adhere to the exposed subendothelium, become activated and release mediators such as TXA 2 and nucleotides stored at very high concentration in the so-called dense granules. Released nucleotides and other soluble agents act in a positive feedback mechanism to cause further platelet activation and amplify platelet responses induced by agents such as thrombin or collagen. Adenine nucleotides act on platelets through three distinct P2 receptors: two are G proteincoupled ADP receptors, namely the P2Y 1 and P2Y 12 receptor subtypes, while the P2X 1 receptor ligand-gated cation channel is activated by ATP. The P2Y 1 receptor initiates platelet aggregation but is not sufficient for a full platelet aggregation in response to ADP, while the P2Y 12 receptor is responsible for completion of the aggregation to ADP. The latter receptor, the molecular target of the antithrombotic drugs clopidogrel, prasugrel and ticagrelor, is responsible for most of the potentiating effects of ADP when platelets are stimulated by agents such as thrombin, collagen or immune complexes. The P2X 1 receptor is involved in platelet shape change and in activation by collagen under shear conditions. Each of these receptors is coupled to specific signal transduction pathways in response to ADP or ATP and is differentially involved in all the sequential events involved in platelet function and haemostasis. As such, they represent potential targets for antithrombotic drugs.

show abstract

Factors responsible for ADP-induced release reaction of human platelets

Cited by 340 publications

References 0 publications

Interrelations of Platelet Aggregation and Secretion

Interrelations of Platelet Aggregation and Secretion

Aspirin and Clopidogrel

P2 receptors and platelet function

Contact Info

Product

Resources

About