Inhibition by naloxone of promoter activity of the neurofilament gene in SK-N-SH cells

Chronic administration of morphine is known to decrease the levels of neuro filaments (NFs) in the ventral tegmental area. We ligated a promoter region of the mouse 68-KDa neurofilament (NF-68) gene to the pGL3-enhancer vector containing a luciferase gene, transfected it into SK-N-SH cells and then a nalyzed transcriptional activity in the cells treated with agonists or anta gonists of opiate receptors. The activity of the NF-68 promoter was suppres sed by naloxone about 55% at 10(-5) M and 30% at 10(-7) M at 48 h, but supp ressed not by morphine. Naltrexone at 10(-5) M suppressed the promoter acti vity about 20%, but levallorphan, DAMGO, DPDPE and U50488 did not. The inhi bition by naloxone was dose-dependent and not reversed by morphine. The inh ibitory effect of naloxone was not observed in N18TG-2 cells and PC12 cells . Experiments with various deletion mutants revealed that a region responsi ble for naloxone suppression spans from - 328 to - 101 in the gene. These r esults suggest that naloxone has the ability to suppress transcriptional ac tivity in some neurons.