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Leishmania sp.:Growth and Survival Are Impaired by Ion Channel Blockers

1998; Elsevier BV; Volume: 88; Issue: 1 Linguagem: Inglês

10.1006/expr.1998.4200

1090-2449

Alicia Ponte‐Sucre, Yelitza Campos, M. Cristina Fernández, Heidrun Moll, Alexis Mendoza-León,

Trypanosoma species research and implications

In the present work we examined the effect of ion transport blockers on the growth and viability ofLeishmania sp.and on the infection of macrophages by the parasite. 4-aminopyridine and glibenclamide block voltage-dependent and K+ATP channels, respectively; amiloride is used to detect Na+channels and Na+/H+antiporters; and anthracene-9-carboxylic acid affects chloride channels. The EC50for promastigote cultures of three strains of theLeishmaniasubgenus, namely,Leishmania (Leishmania)NR,Leishmania (Leishmania) amazonensisLTB0016, andLeishmania (Leishmania) major,at their stationary phase of growth, were, respectively, 39, 46, and 464 μMfor 4-aminopyridine; 7, 0.8, and 10 μMfor glibenclamide and 66, 170, and 10 μMfor anthracene-9-carboxylic acid. The amiloride EC50for NR was 264 μMand 10 μMforL. (L.) major,but was never reached for LTB0016. Higher concentrations of the drugs impaired the exponential growth ofLeishmaniapromastigotes. These results suggest the susceptibility ofLeishmania sp.to blockers associated with K+and Cl−and to Na+or Na+/H+transport systems. Blockade of such systems might have impaired the survival of the parasites as promastigotes. In addition, it affected the persistence of parasites in host cells. Although the infection of the macrophage cell line J774 and peritoneal-exudate macrophages was not significantly decreased by concentrations of the drugs around the promastigotes' EC50, the survival of intracellular parasites decreased significantly in the presence of these drugs without affecting the viability of the macrophages. Some blockers consistently gave small EC50and significantly decreased the infection process as well as the survival of intracellular parasites. Thus, elucidation of their mechanism of action inLeishmaniais relevant, since they could represent a potential subject for the development of leishmanicidal drugs.