Assuntos
Apoptose/efeitos dos fármacos , Oligomicinas/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Leucemia P388/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Ratos , Ratos Wistar , Timo/citologia , Timo/efeitos dos fármacosRESUMO
A natural complex of avermectins, aversectin C, and a component of this complex, avermectin A1, were shown to change the conductivity of Ca2+-dependent Cl- channels of plasmalemma of Chara corallina cells by acting from the outer side of the cellular membrane. Low concentrations of aversectin C and avermectin A1 increased the Cl- current: K1/2 = 35 ng/ml for the whole complex and K1/2 = 21 pg/ml for A1. Relatively high concentrations of the compounds suppressed the Cl- current: K1/2 = 2.2 microg/ml for aversectin C and K1/2 = 4.2 ng/ml for A1. The Hill coefficient for the interaction of avermectin A1 with the corresponding targets was identical for stimulation and suppression of the Cl- current: 2.8 and 2.5, respectively. Bicuculline, a nonspecific inhibitor of the GABAa receptors, did not influence stimulation of Cl- currents caused by low concentrations of avermectins, but at the same time blocked suppression of the Cl- currents by high concentrations of avermectins. Avermectins A2, B1, B2, abamectin and 22,23-dihydroavermectin B1 (ivermectin) did not affect the Cl- currents of Chara corallina cells.
Assuntos
Cálcio/metabolismo , Membrana Celular/fisiologia , Canais de Cloreto/efeitos dos fármacos , Cloretos/metabolismo , Ivermectina/farmacologia , Canais de Cloreto/metabolismo , Cloretos/fisiologia , Relação Dose-Resposta a Droga , Eletrofisiologia , Eucariotos , Ivermectina/análogos & derivados , Técnicas de Patch-ClampRESUMO
A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.
