NF-kappaB, nitric oxide and opiate signaling.

NF-kappaB, a DNA binding factor, has been implicated in inflammatory cytokine activation. NF-kappaB is activated by IkappaBalpha, its inhibitor, which is phosphorylated and proteolytically degraded. In this regard, NF-kappaB is also responsive to reactive oxygen intermediates and calcium. Reports also have emerged that demonstrate that nitric oxide inhibits NF-kappaB transcriptional activation in a variety of cells, including monocytes and endothelial cells. Recently, we have demonstrated that morphine, not opioid peptides, via the mu3 opiate receptor is coupled to constitutive nitric oxide release in these same cells. In this regard, we provide a scenario whereby morphine modulates NF-kappaB activation via nitric oxide. This pathway appears to be the key step in regulating inducible nitric oxide synthase expression, controlling the balance between constitutive nitric oxide synthase and the inducible form.