RESUMO
The effects of the Nothrombel on the formation of platelet-leukocyte complexes (PLCs) induced by thrombin was studied. It was shown, that Nothrombel dose-dependently inhibited the formation of PLCs. Its activity is higher than the activity of the comparison compounds Aspirin. The half maximal effective concentration (EC50) for Nothrombel is 1.75 mMol/mL, for Aspirin is much more than 2.5 mMol/mL. The inhibition mechanism of the PLCs formation by Nothrombel caused by the ability of this drug to inhibit the P-selectin translocation on the platelet membrane, the expression of membrane complex GPIb-IX-V, the mobilization of cytoplasmic calcium in platelets, as well as, apparently, its inhibitory effect on platelet P2Y12 purine receptors.
Assuntos
Plaquetas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Piperazinas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Trombina/antagonistas & inibidores , Adulto , Plaquetas/citologia , Plaquetas/metabolismo , Cálcio/isolamento & purificação , Cálcio/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Leucócitos/citologia , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Selectina-P/genética , Selectina-P/metabolismo , Piperazinas/síntese química , Inibidores da Agregação Plaquetária/síntese química , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Cultura Primária de Células , Receptores Purinérgicos P2Y12/genética , Receptores Purinérgicos P2Y12/metabolismo , Transdução de Sinais , Trombina/farmacologiaRESUMO
The influence of Nothrombel on the expression of membrane complex GPIb-IX-V of platelets activated by thrombin was studied. It is established that Nothrombel reduced thrombin-induced expression of complex GPIb-IX-V on the membrane of the activated platelets. The inhibitory activity of Nothrombel on the expression of GPIb (CD42b) was comparable to its activity with respect to GPIX (CD42a) and is equal to 43 %. With regard to GPV (CD42d) inhibitory effect of the drug was less pronounced and is equal to 22 %. The possible targets for Nothrombel are activation of thromboxane signaling pathway, as well as GPIb-IX-V receptors of platelets itself.
