5-Chloro-7-iodo-8-hydroxyquinoline (clioquinol) inhibits the nerve growth factor-induced stimulation of RNA synthesis in neonatal rat superior cervical ganglion, in vitro--comparison with effects of methylmercuric chloride and 4-hydroxyaminoquinoline-N-oxide

Hori, S.; Kayanuma, K.; Ohtani, S.; Sugiura, H.; Tsubaki, T.

Journal of Toxicological Sciences 12(2): 97-109


ISSN/ISBN: 0388-1350
PMID: 2442409
Accession: 004543803

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The inhibitory effects of 5-chloro-7-iodo-8-hydroxy-quinoline (clioquinol), methylmercuric chloride and 4-hydroxyaminoquinoline-N-oxide(4-HAQO) on DNA, RNA and protein synthesis in the neonatal rat superior cervical ganglion (SCG) were studied in relation to the action of mouse 2.5S nerve growth factor (NGF), using organ cultures. RNA and protein synthesis in SCG were stimulated approximately 3- and 2-fold, respectively, by NGF (1 .mu.g/ml), but the DNA synthesis was only slightly or not at all stimulated. Methylmercuric chloride and 4-HAQO dose-dependently inhibited DNA, RNA and protein synthesis, either in the presence or in the absence of NGF. On the other hand, clioquinol (up to 100 .mu.M) slightly or not at all inhibited RNA synthesis in the absence of NFG; however, it did abolish the NGF-induced stimulation of RNA synthesis in the presence of NGF. The DNA and protein synthesis were dose-dependently inhibited by clioquinol, either in the presence or in the absence of NGF. We conclude from this study that the interaction between clioquinol and the functions of NGF raises the question of a possible toxicity of the drug on specific neurons.