Transcriptional regulation and cell specificity determinants of the rat nicotinic acetylcholine receptor alpha 3 gene

The effects of increased cAMP level and reduced protein kinase C activity on transcription of the alpha 3 neuronal nicotinic acetylcholine receptor (nAChR) gene in PC12 cells were examined. Two nAChR alpha 3 transcripts (3.9 and 2.4 kb) are expressed in PC12 cells. When PC12 cells were grown in 2 mu m phorbol 12-myristate 13-acetate (PMA) for 2 days to lower protein kinase C activity, the levels of both transcripts were increased. When PC12 cells were grown in 5 mu m forskolin, the level of the 3.9 kb transcript was increased. We previously constructed clones containing promoter elements located upstream of the alpha 3 gene which allow reporter gene expression in PC12 cells. These constructs were transfected into PC12 cells grown in PMA or forskolin. The increase in alpha 3 transcripts in response to PMA or forskolin was shown to be mediated at least in part at the transcriptional level by elements located within 600 nucleotides of the transcriptional start sites. The promoter constructs were also used to demonstrate that elements needed to restrict the expression of alpha 3 in non-neuronal cells lie near to the 5' end of the alpha 3 gene.