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Biol Chem ; 384(9): 1333-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14515997

RESUMO

Hementerin (HT) is an 80 kDa fibrino(geno)lytic metalloprotease, purified from saliva of the leech Haementeria depressa. In the present report, the effect of HT on several functional parameters of human platelets was assessed. HT inhibited platelet aggregation and ATP release induced by different agonists such as ADP, adrenaline, collagen, thrombin, and arachidonic acid. HT did neither modify the expression of platelet glycoproteins (Ib, IIb-IIIa, Ia-IIa, IV) nor intraplatelet fibrinogen levels, whereas it markedly decreased CD62P and CD63 levels after the stimulation with thrombin. HT significantly increased thrombin-induced platelet Ca2+ intracellular levels, cGMP content and nitric oxide synthase (NOS) activity. The effect of HT on platelet aggregation was reversed by two NOS inhibitors, N(omega)-Nitro-L-arginine methyl ester and 2 N(G)-Nitro-L-arginine. In summary, these results indicate that HT is an effective inhibitor of human platelet aggregation, presumably through activation of the platelet's nitridergic pathway.


Assuntos
Sanguessugas/enzimologia , Óxido Nítrico/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Extratos de Tecidos/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , GMP Cíclico/metabolismo , Fibrinogênio/análise , Metaloproteases/farmacologia , Óxido Nítrico Sintase/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Glicoproteínas da Membrana de Plaquetas/efeitos dos fármacos , Trombina/farmacologia
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