Oncocalyxone A inhibits human platelet aggregation by increasing cGMP and by binding to GP Ibα glycoprotein
| Autor: | 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, Mirta Ana, Chudzinski Tavassi, A. M. |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Blood Platelets Male CIENCIAS MÉDICAS Y DE LA SALUD Adolescent Platelet Aggregation ANTIPLATELET ACTIVITY Anthraquinones Medicina Clínica In Vitro Techniques Nitric Oxide HUMAN PLATELETS Thromboxane A2 Adenosine Triphosphate purl.org/becyt/ford/3.2 [https] Cyclic AMP Humans AUXEMMA ONCOCALYX Cyclic GMP ONCOCALYXONE Cyclic Nucleotide Phosphodiesterases Type 5 Middle Aged Flow Cytometry Research Papers Adenosine Diphosphate Platelet Glycoprotein GPIb-IX Complex Guanylate Cyclase purl.org/becyt/ford/3 [https] Female Medicina Critica y de Emergencia QUINONES Platelet Aggregation Inhibitors Protein Binding |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | 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 μM) 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-μM) 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. © 2008 Nature Publishing Group All rights reserved. Fil: Ferreira, M. A. D.. Universidade Estadual do Ceará; Brasil Fil: Do Nascimento, N. R. F.. Universidade Estadual do Ceará; Brasil Fil: De Sousa, C. M.. Universidade Estadual do Ceará; Brasil Fil: Pessoa, O. D. L.. Universidade Estadual do Ceará; Brasil Fil: De Lemos, T. L. G.. Universidade Estadual do Ceará; Brasil Fil: Ventura, J. S.. Butantan Institute; Brasil Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Chudzinski Tavassi, A. M.. Butantan Institute; Brasil |
| Databáze: | OpenAIRE |
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