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.
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 syntheses 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 syntheses in SCG were stimulated approximately 3- and 2-fold, respectively, by NGF (1 microgram/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 syntheses, either in the presence or in the absence of NGF. On the other hand, clioquinol (up to 100 microM) slightly or not at all inhibited RNA synthesis in the absence of NGF; however, it did abolish the NGF-induced stimulation of RNA synthesis in the presence of NGF. The DNA and protein syntheses 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.
D015108:4-Hydroxyaminoquinoline-1-oxide / Q000633:toxicity*; D000634:Aminoquinolines / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D007464:Clioquinol / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000378:metabolism; D006912:Hydroxyquinolines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008767:Methylmercury Compounds / Q000633:toxicity*; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D000634:Aminoquinolines; D006912:Hydroxyquinolines; D008767:Methylmercury Compounds; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D015108:4-Hydroxyaminoquinoline-1-oxide; D012313:RNA; D007464:Clioquinol; D004247:DNA; C004925:methylmercuric chloride