Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo de estudio
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Atherosclerosis ; 191(2): 250-8, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16797553

RESUMEN

Sanguinarine is a plant alkaloid present in the root of Sanguinaria canadensis and Poppy fumaria species. Sanguinarine has been used as an antiseptic mouth rinse and a toothpaste additive to reduce dental plaque and gingival inflammation. In this study, we investigated the antiplatelet effects of sanguinarine, aiming to extend its potential pharmacological applications. Sanguinarine inhibited platelet aggregation induced by arachidonic acid (AA), collagen, U46619 and sub-threshold concentration of thrombin (0.05 U/ml) with IC(50) concentrations of 8.3, 7.7, 8.6 and 4.4 microM, respectively. Sanguinarine (5-10 microM) inhibited 10-31% of platelet TXB(2) production, but not platelet aggregation induced by higher concentration of thrombin (0.1 U/ml). SQ29548, a thromboxane receptor antagonist, inhibited the AA-induced platelet aggregation but not TXB(2) production. Sanguinarine suppressed cyclooxygenase-1 (COX-1) activity (IC(50)=28 microM), whereas its effect on COX-2 activity was minimal. Sanguinarine (8, 10 microM) further inhibited the AA-induced Ca(2+) mobilization by 27-62%. In addition, SQ22536, an adenylate cyclase inhibitor, attenuated the inhibitory effect of sanguinarine toward AA-induced platelet Ca(2+) mobilization and aggregation. These results suggest that sanguinarine is a potent antiplatelet agent, which activates adenylate cyclase, inhibits platelet Ca(2+) mobilization, TXB(2) production as well as suppresses COX-1 enzyme activity. Sanguinarine may have therapeutic potential for treatment of cardiovascular diseases related to platelet aggregation.


Asunto(s)
Alcaloides/farmacología , Benzofenantridinas/farmacología , Plaquetas/efectos de los fármacos , Calcio/metabolismo , AMP Cíclico/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Isoquinolinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Tromboxano B2/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Adenilil Ciclasas/metabolismo , Animales , Ácido Araquidónico/farmacología , Plaquetas/metabolismo , Colágeno/farmacología , Ciclooxigenasa 1/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Técnicas In Vitro , Conejos , Receptores de Tromboxanos/efectos de los fármacos , Receptores de Tromboxanos/metabolismo , Trombina/farmacología
2.
Semin Thromb Hemost ; 26(1): 43-5, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10805281

RESUMEN

A platelet disorder characterized by the absence of thromboxane A2 (TXA2)-induced platelet aggregation is a new clinical entity of platelet dysfunction. The platelets of three patients had the ability to bind exogenous TXA2, but synthetic TXA2 mimetic-induced postreceptor biochemical events, such as IP3 formation, Ca2+ mobilization, phosphatidic acid formation, and GTPase activities, were selectively defective, suggesting impaired coupling between the TXA2 receptor and phospholipase C activation. Gene analysis of the TXA2 receptor showed a substitution of Leu for Arg60 in the first cytoplasmic loop in all patients, and this mutation seemed to be responsible for this platelet disorder.


Asunto(s)
Sustitución de Aminoácidos , Plaquetas/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Trastornos Hemorrágicos/genética , Agregación Plaquetaria/efectos de los fármacos , Mutación Puntual , Receptores de Tromboxanos/genética , Tromboxano A2/fisiología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Animales , Plaquetas/metabolismo , Células CHO , Calcimicina/farmacología , Codón/genética , Cricetinae , Cricetulus , ADN Complementario/genética , Activación Enzimática , GTP Fosfohidrolasas/metabolismo , Humanos , Ácidos Fosfatidicos/biosíntesis , Fosfatidilinositol Diacilglicerol-Liasa , Receptores de Tromboxanos/efectos de los fármacos , Receptores de Tromboxanos/fisiología , Proteínas Recombinantes/metabolismo , Fluoruro de Sodio/farmacología , Tromboxano A2/análogos & derivados , Tromboxano A2/farmacología , Transfección , Fosfolipasas de Tipo C/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA