2-Aminopurine inhibits RNA and protein synthesis and reduces catecholamine desensitization in C6-2B rat glioma cells.
We previously proposed that intracellular cyclic AMP accumulation induces a putative, rapidly turning over protein inhibitory to further hormone activation of adenylate cyclase. In the present study, 2-aminopurine, which has been reported to selectively block c-fos gene expression, was used to test the hypothesis that c-fos protein might be involved in the desensitization to catecholamines was observed in 2-aminopurine-treated C6-2B rat glioma cells. However, we found 2-aminopurine to inhibit, in a concentration-dependent manner, total cellular RNA and protein synthesis in C6-2B, HeLa, Swiss 3T3 and BALB/c cells. mRNA synthesis was also markedly reduced in 2-aminopurine-treated cells. These unexpected findings, while supporting our hypothesis of a protein synthesis-sensitive step in the development of refractoriness, raise concern about the specificity of action of 2-aminopurine to inhibit c-fos induction and thus any cellular process, including desensitization, which might be regulated by c-fos gene expression.
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20007.
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DeBernardi
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D015075:2-Aminopurine / Q000494:pharmacology*; D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D005910:Glioma; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014529:Uridine / Q000378:metabolism
D002395:Catecholamines; D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D005576:Colforsin; D015075:2-Aminopurine; D012313:RNA; D003994:Bucladesine; D008715:Methionine; D000242:Cyclic AMP; D007545:Isoproterenol; D014529:Uridine