2-Aminopurine inhibits RNA and protein synthesis and reduces catecholamine desensitization in C6-2B rat glioma cells

• Published in: FEBS letters 1992-01, Vol.296 (1), p.112-116
• Main Authors: DeBernardi, Maria A., Brooker, Gary
• Format: Article
• Language: English
• Subjects: 2-aminopurine; 2-Aminopurine - pharmacology; 2-AP; 3-isobutyl-l-methylxanthine; 3T3 Cells - drug effects; Animals; Biological and medical sciences; Bt2cAMP; Bucladesine - pharmacology; c- fos; Catecholamines - metabolism; Cell biosynthesis; Cell physiology; Colforsin - pharmacology; Cyclic AMP - metabolism; Drug Interactions; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Glioma; HeLa Cells - drug effects; Humans; IBMX; Isoproterenol - pharmacology; Methionine - metabolism; Mice; Mice, Inbred BALB C; Molecular and cellular biology; N 0,O2′-dibutyryladenosine 3′,5′-cyclic monophosphate; Protein Biosynthesis; Protein Synthesis Inhibitors - pharmacology; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Rats; Refractoriness; Responses to growth factors, tumor promotors, other factors; RNA - biosynthesis; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Tumor Cells, Cultured - drug effects; Uridine - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(92)80415-D

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 process. Indeed, a reduction in heterologous 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/e 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.