Effects of a P2Y12 receptor antagonist on the response of equine platelets to ADP. Comparison with human platelets

Mateos-Trigos, G.; Evans, Richard J.; Heath, M. F.

doi:10.1016/s0034-5288(02)00096-6

Cited by 15 publications

(7 citation statements)

References 28 publications

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“…The platelet shape change in response to ADP is mediated by the P2Y 1 receptor, while the aggregation response is mediated by the P2Y 12 receptor, the target of clopidogrel 28 . While the P2Y 1 receptor is responsible for the initial rate of platelet aggregation in humans, prior reports suggest that the P2Y 12 receptor also contributes to this function in the horse 29 . The lack of a significant change in the slope of aggregation in this study does not support this conclusion.…”

Section: Discussioncontrasting

confidence: 90%

Effects of Clopidogrel and Aspirin on Platelet Aggregation, Thromboxane Production, and Serotonin Secretion in Horses

Brainard

Epstein

LoBato

et al. 2010

Veterinary Internal Medicne

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Background: Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation.Objectives: To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. Animals: Six healthy adult horses. Methods: Horses received clopidogrel (2 mg/kg PO q24h) or ASA (5 mg/kg PO q24h) for 5 days in a prospective randomized cross-over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B 2 (TXB 2 ) by ELISA were evaluated. In horses receiving clopidogrel, high-performance liquid chromatography analysis for clopidogrel and its carboxylic-acid metabolite SR 26334 was performed.Results: SR 26334 was identified in all clopidogrel-treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP-induced platelet aggregation persisting for 120 hours after the final dose. ADP-induced platelet aggregation decreased from a baseline of 70.2 AE 14.7% to a minimum of 15.9 AE 7.7% 24 hours after the final dose (P o .001). Collagen-induced aggregation decreased from a baseline of 93 AE 9.5% to a minimum of 70.8 AE 16.9% 48 hours after the final dose (P o .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB 2 from a baseline value of 1310 AE 1045 to 128 AE 64 pg/mL within 24 hours (P o .01).Conclusions and Clinical Importance: Clopidogrel effectively decreases ADP-induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.

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Section: Discussioncontrasting

confidence: 90%

Effects of Clopidogrel and Aspirin on Platelet Aggregation, Thromboxane Production, and Serotonin Secretion in Horses

Brainard

Epstein

LoBato

et al. 2010

Veterinary Internal Medicne

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“…As previously demonstrated in human platelets [35], ADP-induced aggregation involves two ADP-receptor subtypes (P2Y 1 and P2Y 12 ). These receptors were also described on equine platelets [36][37][38].…”

Section: Discussionmentioning

confidence: 82%

Age-Related Developmental Clotting Profile and Platelet Aggregation in Foals Over the First Month of Life

Piccione

Arfuso

Quartuccio

et al. 2015

Journal of Equine Veterinary Science

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“…Meyers et al showed that bovine platelets respond to thrombin and arachidonic acid more weakly than do human platelets [29]. Equine and camelid platelets aggregate less than human platelets upon stimulation with ADP [30, 32]. Interestingly, adrenaline and arachidonic acid did not cause aggregation of platelets from either species [31, 32].…”

Section: Discussionmentioning

confidence: 99%

Protein expression in platelets from six species that differ in their open canalicular system

2010

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Platelets contain an invaginated, tubular membranous structure called the surface-connected open canalicular system (SCCS or OCS), which is contiguous with the plasma membrane and serves as a site for granule fusion and as a reservoir of membrane for platelet spreading. According to ultrastructural studies, platelets from some species lack OCS. In an attempt to correlate biochemical and functional attributes with the presence of an OCS, platelets from human, mouse and dog (OCS+), and from cow, camel and horse (OCS−) were analysed for differential protein expression and aggregation in response to thrombin. Among the 18 different cytoskeletal and regulatory proteins examined, five (Rac1, RhoA, Ras, calmodulin and Src) were expressed at higher levels in OCS+ platelets (p<0.05). Given the role of Arf6 in the formation of tubular invaginations in nucleated cells, the levels of Arf6-GTP were analysed in OCS+ and OCS− platelets. There was no significant correlation between the presence of OCS and total Arf6 or Arf6-GTP levels. Comparison of platelet aggregation between different species suggests that OCS− platelets have delayed responses. This comparison of platelets from six different species, which differ in their OCS, shows the differential expression of known signaling components and foreshadows future studies focusing on OCS formation and function.

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Effects of a P2Y12 receptor antagonist on the response of equine platelets to ADP. Comparison with human platelets

Cited by 15 publications

References 28 publications

Effects of Clopidogrel and Aspirin on Platelet Aggregation, Thromboxane Production, and Serotonin Secretion in Horses

Effects of Clopidogrel and Aspirin on Platelet Aggregation, Thromboxane Production, and Serotonin Secretion in Horses

Age-Related Developmental Clotting Profile and Platelet Aggregation in Foals Over the First Month of Life

Protein expression in platelets from six species that differ in their open canalicular system

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