Nuclear factor kappaB signaling in opioid functions and receptor gene expression.
Opiates are the most powerful of all known analgesics. The prototype opiate morphine has been used as a painkiller for several thousand years. Chronic usage of opiates not only causes drug tolerance, dependence, and addiction, but also suppresses immune functions and affects cell proliferation and cell survival. The diverse functions of opiates underscore the complexity of opioid receptor signaling. Several downstream signaling effector systems, including adenylyl cyclase, mitogen-activated protein kinase, Ca2+ channels, K+ channels, and phosphatidylinositol 3-kinase/Akt, have been identified to be critical in opioid functions. Nuclear factor-kappaB (NF-kappaB), one of the most diverse and critical transcription factors, is one of the downstream molecules that may either directly or indirectly transmit the receptor-mediated upstream signals to the nucleus, resulting in the regulation of the NF-kappaB-dependent genes, which are critical for the opioid-induced biological responses of neuronal and immune cells. In this minireview, we focus on current understanding of the involvement of NF-kappaB signaling in opioid functions and receptor gene expression in cells.
Chen
Yulong L
YL
Department of Pharmacology, the University of Minnesota School of Medicine, 321 Church St. S.E., Minneapolis, MN 55455, USA. chenx112@umn.edu
Law
Ping-Yee
PY
Loh
Horace H
HH
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D000701:Analgesics, Opioid; D016328:NF-kappa B; D011957:Receptors, Opioid