Gramicidin toxicity in NG108-15 cells: protective effects of acetamidine and guanidine.

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 x glioma hybrid) cells. Specifically, intracellular microelectrode techniques were employed to examine changes in membrane resting potential (Vm) and input resistance (Rin). At 1 micromol/L, ACE significantly reduced loss of Vm induced by 1 or 10 microg/ml GRAM, although higher concentrations of ACE did not afford enhanced antagonism. GUAN, in contrast, produced a concentration-dependent antagonism of GRAM-induced Vm and Rin loss, with high concentrations (10 or 100 micromol/L) completely preventing diminutions in both Vm and Rin. In control cells superfused without GRAM, ACE produced a direct, concentration-dependent reduction in Vm and Rin, whereas GUAN hyperpolarized NG108-15 cells but did not alter Rin. These data represent the initial demonstration of the reversal of GRAM toxicity in an intact cell system.

• Authors: J A Doebler
• Journal: Cell biology and toxicology (Cell Biol Toxicol) Vol. 15 Issue 5 Pg. 279-89 ( 1999) ISSN: 0742-2091 [Print] Netherlands
• PMID: 10813361 (Publication Type: Journal Article)

Chemical References

• Amidines
• Anti-Bacterial Agents
• Neuroprotective Agents
• Parasympathomimetics
• Trypsin Inhibitors
• Gramicidin
• Guanidine
• acetamidine

Topics

• Amidines (pharmacology)
• Animals
• Anti-Bacterial Agents (toxicity)
• Drug Interactions
• Electric Impedance
• Electrophysiology
• Glioma
• Gramicidin (toxicity)
• Guanidine (pharmacology)
• Hybrid Cells (drug effects, physiology)
• Membrane Potentials (drug effects)
• Neuroblastoma
• Neurons (drug effects)
• Neuroprotective Agents (pharmacology)
• Parasympathomimetics (pharmacology)
• Rats
• Trypsin Inhibitors (pharmacology)