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Oncocalyxone A inhibits human platelet aggregation by increasing cGMP and by binding to GP Ibα glycoprotein
Author(s) -
Ferreira M A D,
Do Nascimento N R F,
De Sousa C M,
Pessoa O D L,
De Lemos T L G,
Ventura J S,
Schattner M,
ChudzinskiTavassi A M
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.199
Subject(s) - ristocetin , chemistry , platelet , sodium nitroprusside , thrombin , von willebrand factor , adenosine diphosphate , fibrinogen , biochemistry , platelet activation , pharmacology , nitric oxide , medicine , platelet aggregation , biology , organic chemistry
Background and purpose: Oncocalyxone A (OncoA) has a concentration‐dependent anti‐platelet activity. The present study aimed to further understand the mechanisms related to this effect. Experimental approach: Human platelet aggregation was measured by means of a turbidimetric method. OncoA (32–256 μ M ) was tested against several platelet‐aggregating agents, such as adenosine diphosphate (ADP), collagen, arachidonic acid (AA), ristocetin and thrombin. Key results: OncoA completely inhibited platelet aggregation with a calculated mean inhibitory concentration (IC 50 ‐μ M ) of 122 for ADP, 161 for collagen, 159 for AA, 169 for ristocetin and 85 for thrombin. The anti‐aggregatory activity of OncoA was not inhibited by 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). OncoA, at a concentration that caused no significant anti‐aggregatory activity, potentiated sodium nitroprusside (SNP) anti‐aggregatory activity (18.8±2.9%‐SNP vs 85.0±8.2%‐SNP+OncoA). The levels of nitric oxide (NO) or cAMP were not altered by OncoA while cGMP levels were increased more than 10‐fold by OncoA in resting or ADP‐activated platelets. Flow cytometry revealed that OncoA does not interact with receptors for fibrinogen, collagen or P‐selectin. Nevertheless, OncoA decreased the binding of antibodies to GP Ibα, a glycoprotein that is related both to von Willebrand factor and to thrombin‐induced platelet aggregation. Conclusion and implications: OncoA showed anti‐aggregatory activity in platelets that was associated with increased cGMP levels, not dependent on NO and with blocking GP Ibα glycoprotein. This new mechanism has the prospect of leading to new anti‐thrombotic drugs. British Journal of Pharmacology (2008) 154 , 1216–1224; doi: 10.1038/bjp.2008.199 ; published online 2 June 2008