LEISHMANIA SP - GROWTH AND SURVIVAL ARE IMPAIRED BY ION-CHANNEL BLOCKERS

In the present work we examined the effect of ion transport blockers o n the growth and viability of Leishmania sp. and on the infection of m acrophages by the parasite. 4-aminopyridine and glibenclamide block vo ltage-dependent and K+ ATP channels, respectively; amiloride is used t o detect Na+ channels and Na+/H+ antiporters; and anthracene-9-carboxy lic acid affects chloride channels. The EC50 for promastigote cultures of three strains of the Leishmania subgenus, namely, Leishmania (Leis hmania) NR, Leishmania (Leishmania) amazonensis LTB0016, and Leishmani a (Leishmania) major, at their stationary phase of growth, were, respe ctively, 39, 46, and 464 mu M for 4-aminopyridine; 7, 0.8, and 10 mu M for glibenclamide and 66, 170, and 10 mu M for anthracene-9-carboxyli c acid. The amiloride EC50 for NR was 264 mu M and 10 mu M for L. (L.) major, but was never reached for LTB0016. Higher concentrations of th e drugs impaired the exponential growth of Leishmania promastigotes. T hese results suggest the susceptibility of Leishmania sp. to blockers associated with K+ and Cl- and to Na+ or Na+/H+ transport systems. Blo ckade of such systems might have impaired the survival of the parasite s as promastigotes. In addition, it affected the persistence of parasi tes in host cells. Although the infection of the macrophage cell line J774 and peritoneal-exudate macrophages was not significantly decrease d by concentrations of the drugs around the promastigotes' EC50, the s urvival of intracellular parasites decreased significantly in the pres ence of these drugs without affecting the viability of the macrophages . Some blockers consistently gave small EC50 and significantly decreas ed the infection process as well as the survival of intracellular para sites. Thus, elucidation of their mechanism of action in Leishmania is relevant, since they could represent a potential subject for the deve lopment of leishmanicidal drugs. (C) 1998 Academic Press.