RESUMEN
The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes of Trypanosoma cruzi, at concentrations lower than 100 microM, and motility and infectivity of the bloodstream trypomastigote form at 200 microM. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 microM TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.
Asunto(s)
Mitocondrias/efectos de los fármacos , Trifluoperazina/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Adenosina Trifosfatasas/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Animales , Microscopía Electrónica , Mitocondrias/fisiología , Dilatación Mitocondrial/efectos de los fármacos , Oligomicinas/farmacología , Trypanosoma cruzi/fisiología , Trypanosoma cruzi/ultraestructuraAsunto(s)
Cardiomiopatía Chagásica/fisiopatología , Epinefrina/farmacología , Contracción Miocárdica/efectos de los fármacos , Norepinefrina/farmacología , Propranolol/farmacología , Enfermedad Aguda , Animales , Dibencilcloretamina/farmacología , Epinefrina/antagonistas & inhibidores , Masculino , Ratones , Ratones Endogámicos C3H , Norepinefrina/antagonistas & inhibidoresRESUMEN
Tissue injury (laparotomy) produces an increase in plasma fibrinogen. This increase is inhibited by the removal of the adrenal medulla, but injection of epinephrine in laparotomized-medullectomized rats returns fibrinogen levels to values similar to those observed in only laparotomized rats. Epinephrine administration to laparotomized rats increases the fibrinogen compared with the group of laparotomized rats without treatment, but epinephrine by itself does not modify plasma fibrinogen levels in uninjured rats. Epinephrine is apparently responsible for the increase of plasma fibrinogen in rats subjected to tissue injury, probably through beta adrenergic stimulation.