Abstract
Studies were conducted using a novel in vitro approach to investigate the efficacy of acetamidine hydrochloride (ACE) and guanidine hydrochloride (GUAN), previously shown to block gramicidin D (GRAM) channels in artificial membranes, in preventing the toxic effects of GRAM in NG108-15 (neuroblastoma×glioma hybrid) cells. Specifically, intracellular microelectrode techniques were employed to examine changes in membrane resting potential (V m) and input resistance (R in). At 1 μmol/L, ACE significantly reduced loss of V m induced by 1 or 10 μg/ml GRAM, although higher concentrations of ACE did not afford enhanced antagonism. GUAN, in contrast, produced a concentration-dependent antagonism of GRAM-induced V m and R in loss, with high concentrations (10 or 100 μmol/L) completely preventing diminutions in both V m and R in. In control cells superfused without GRAM, ACE produced a direct, concentration-dependent reduction in V m and R in, whereas GUAN hyperpolarized NG108-15 cells but did not alter R in. These data represent the initial demonstration of the reversal of GRAM toxicity in an intact cell system.
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Doebler, J. Gramicidin toxicity in NG108-15 cells: protective effects of acetamidine and guanidine. Cell Biol Toxicol 15, 279–289 (1999). https://doi.org/10.1023/A:1007651417519
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DOI: https://doi.org/10.1023/A:1007651417519