FS390, a novel microbial metabolite from Streptomyces spp. was identified as a small molecular substance and shown a inhibition activities for the release of neurotransmitter from rat hippocampal neuron and PC12 cells. FS390 is an inhibitor of trifiated norepinephrine ([3H]-NE) release in high K+ buffer solution containing ionomycin, indicating that FS390 inhibits neurotransmitter release after the influx of Ca2+ ions. When examined the effect of FS390 on beta-glucuronidase release from guinea pig neurophils, FS390 inhibited beta-glucuronidas release: when treated with 5 microgram/mL of FS390, which was not induced cellular cytotoxicity. The fact that the beta-glucuronidase release in neutrophil and norepinephrine release in neuron was inhibited suggests the similarity in the locations and the mechanisms of FS390 action targets. When treated with 5 microgram/mL of FS390, [3H]-NE release and neurite extension for both rat hippocampal neurons and PC12 cells were prevented. These observations of FS390 functioning as an inhibitor of neurotransmitter release suggest that FS390 has an important role in synaptic transmission in neuron.
Animals ; Exocytosis* ; Glucuronidase ; Guinea Pigs ; Ionomycin ; Ions ; Neurites* ; Neurons* ; Neurotransmitter Agents ; Neutrophils ; Norepinephrine ; PC12 Cells* ; Rats* ; Streptomyces ; Synaptic Transmission

BACKGROUND: Paraquat causes severe tissue toxicity when ingested, but has no effective treatment modality. We have shown that high dose vitamin C has effective antioxidant activities against the paraquat intoxication in a previous animal experiment. This study was designed to evaluate the effect of antioxidant therapy with high dose vitamin C and vitamin E in human cases of paraquat intoxication. METHODS: From August 1999 to August 2001, 19 paraquat intoxication patients who visited the emergency department of the Seoul National University Hospital and the Kyounghee University Hospital were enrolled to this study. They were devided into two groups, a control group(9 patients) and a study group(10 patients). The control group received only conservative managements including gastro-intestinal decontaminati-on. The study group received conservative managements plus the antioxidant therapy which was composed of vitamin C 24 gm/day intravenously and 20 gm/day orally, and vitamin E 1.6 gm/day orally. RESULTS: In the study group, 5 of 10 patients(50%) survived, but all patients of the control group died(p=0.003). There were no significant differences in age, sex, and usage of gastric lavage and activated charcoal between the two groups. Difference in ingested amount of paraquat between the two groups could not be analyzed due to the inexact and subjective measuring methods based on patients'histories. CONCLUSION: Antioxidant therapy with high dose vitamin C and vitamin E is effective in improving survival rate in paraquat intoxicated patients.
Animal Experimentation ; Ascorbic Acid ; Charcoal ; Emergency Service, Hospital ; Gastric Lavage ; Humans ; Paraquat* ; Seoul ; Survival Rate ; Vitamin E ; Vitamins