Almaghrabi, SY and Geraghty, DP and Ahuja, KDK and Adams, MJ, Vanilloid-like agents inhibit aggregation of human platelets, Thrombosis Research, 134, (2) pp. 412-417. ISSN 0049-3848 (2014) [Refereed Article]
Copyright 2014 Elsevier
Introduction: Plant-derived and endogenous vanilloid-like agents exert their effects on cells through transient receptor potential vanilloid-1 (TRPV1). Little is known about the effects of these agents on platelet aggregation. We investigated the effect of various vanilloid-like agents on in-vitro platelet aggregation and tested whether this action is mediated through TRPV1. Understanding the mechanism of action of these compounds in platelets is important in that these compounds may be developed as novel anti-platelet agents.
Materials and Methods: The effects of plant-derived (capsaicin; dihydrocapsaicin, DHC) and endogenous vanilloid-like agents (N-oleoyldopamine, OLDA; N-arachidonoyl-dopamine, NADA) on platelet aggregation were investigated using ADP (5, 10 μM), collagen (4, 8 μg/mL) and arachidonic acid (AA, 300, 400 μg/mL) as agonists. The direct effects of these agents on platelet viability were also determined using an LDH release assay.
Results: Capsaicin, OLDA and NADA inhibited ADP-induced platelet aggregation in a concentration-dependent manner. OLDA and NADA, but not capsaicin and DHC, inhibited collagen-induced aggregation, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA, but not OLDA. Inhibition of aggregation was not due to direct toxicity of these agents towards platelets. The TRPV1 antagonist, SB-452533, did not affect inhibition of ADP-induced platelet aggregation by capsaicin and OLDA.
Conclusions: These results demonstrate that the endovanilloids, OLDA and NADA, and plant-derived vanilloid, capsaicin, inhibit ADP-induced platelet aggregation. Collagen-induced aggregation was inhibited only by endovanilloids, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA. This inhibition was not due to direct toxic effects of these agents, nor was inhibition of ADP-induced aggregation TRPV1 mediated.
|Item Type:||Refereed Article|
|Keywords:||platelets, vanilloids, aggregation, capsaicin, dihydrocapsaicin, N-oleoyldopamine, N-arachidonoyl-dopamine, TRPV1|
|Research Division:||Medical and Health Sciences|
|Research Group:||Pharmacology and Pharmaceutical Sciences|
|Research Field:||Clinical Pharmacology and Therapeutics|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Blood Disorders|
|Author:||Almaghrabi, SY (Ms Safa Almaghrabi)|
|Author:||Geraghty, DP (Professor Dominic Geraghty)|
|Author:||Ahuja, KDK (Dr Kiran Ahuja)|
|Author:||Adams, MJ (Dr Murray Adams)|
|Web of Science® Times Cited:||3|
|Deposited By:||Health Sciences A|
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