title: Vanilloid-like agents inhibit aggregation of human platelets.
abstract: BACKGROUND
  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.
  
  
  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, 10μM), collagen (4, 8μg/mL) and arachidonic acid (AA, 300, 400μg/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.
authors: School of Health Sciences, University of Tasmania, Bag 1320 Launceston, Tasmania, 7250, Australia.
authors: Safa Y
authors: SY
authors: Almaghrabi
authors: School of Health Sciences, University of Tasmania, Bag 1320 Launceston, Tasmania, 7250, Australia.
authors: Dominic P
authors: DP
authors: Geraghty
authors: School of Health Sciences, University of Tasmania, Bag 1320 Launceston, Tasmania, 7250, Australia.
authors: Kiran D K
authors: KD
authors: Ahuja
authors: School of Health Sciences, University of Tasmania, Bag 1320 Launceston, Tasmania, 7250, Australia. Electronic address: Murray.Adams@utas.edu.au.
authors: Murray J
authors: MJ
authors: Adams
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D010944:Plants / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; D010975:Platelet Aggregation Inhibitors; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C474941:arachidonyl dopamine; D000244:Adenosine Diphosphate; D002211:Capsaicin; C488796:N-oleoyldopamine; D004298:Dopamine; C012906:dihydrocapsaicin
keywords: Capsaicin; Dihydrocapsaicin; N-arachidonoyl-dopamine; N-oleoyldopamine; TRPV1