REGULATION OF STRIATAL PROENKEPHALIN AND PRODYNORPHIN GENE-EXPRESSIONBY TRANSCRIPTION FACTOR CREB

There has been controversy over the precise mechanisms by which neural stimuli acting via cAMP and Ca2+ pathways regulate expression of the genes encoding the opioid peptide precursors proenkephalin and prodyno rphin. Evidence has been adduced for both AP-1 proteins, including Fos , and CREB-like proteins as the key factors transducing signals to the DNA. Here we present evidence from in vivo systems that CREB, rather than Fos, is likely the key protein regulating cAMP responsiveness of these two opioid genes. In addition, we show that CREB is phosphorylat ed in vivo in response to stimuli known to regulate these opioid genes .