Signal Transduction Induced by Opioids in Immune Cells: A Review

Abstract

New data regarding signal transduction triggered by opioid ligands in immune cells are reviewed, and the signal transduction in neuronal cells is documented. Similar signaling pathways are induced by opioids in immune as well as neuronal cells. Opioids altered second messenger cAMP, intracellular calcium, and second messenger-induced kinases in immune cells. Met-enkephalin, preferentially δ-opioid, was bimodally regulated, while ĸ-opioids inhibited these second messengers. δ-, ĸ- and µ-opioids altered nitric oxide secretion, inducing cGMP as the second messenger in immune cells. Coupling of opioid agonists to opioid receptors activated mitogen-activated protein/extracellular signal-regulated protein kinases and various transcription factors in immune cells. Activator protein 1 (AP-1), c-fos, and nuclear factor-ĸB (NF-ĸB) are transcription factors shared by neuronal and immune cells. δ-Opioids activated AP-1, c-fos, activating transcription factor 2, Ikaros-1 and Ikaros-2 transcription factors in immune cells. Induction of ĸ-opioid receptor gene by retinoic acid resulted in increased binding of Sp1 transcription factor to the promoter of the ĸ-opioid receptor. µ-Opioids inhibited synthesis of common transcription factors AP-1, c-fos, NF-ĸB, and nuclear factor of activated T cells in activated or stimulated immune cells, whereas µ-opioids activated NF-ĸB, GATA-3, and Kruppel-like factor 7 transcription factors in non-stimulated immune cells.