Endogenous opioid systems

Abstract

DRG= : dorsal root ganglion; GABA= : γ-aminobutyric acid; GPCR= : G-protein-coupled receptor; Leu= : leucine; LID= : levodopa-induced dyskinesia; Met= : methionine; NOP= : nociceptin receptor; PAG= : periaqueductal gray; PD= : Parkinson disease; PDYN= : preprodynorphin; PENK= : preproenkephalin; Phe= : phenylalanine; PNOC= : pronociceptin; POMC= : proopiomelanocortin; RVM= : rostral ventromedial medulla; VTA= : ventral tegmental area The endogenous opioid system consists of 3 families of opioid peptides, β-endorphin, enkephalins, and dynorphins, and 3 families of receptors, μ (MOR), δ (λ, DOR), and κ (KOR). Opioid peptides and their receptors have a widespread but selective distribution in the central and peripheral nervous systems, particularly in circuits involved in pain modulation, reward, responses to stress, and autonomic control. Whereas opioid receptor activation elicits presynaptic and postsynaptic inhibition, the differential expression and strategic localization of the different opioid receptor subtypes in projection neurons and local inhibitory interneurons provides for a wide range of opioid-induced behavioral effects. The opioid system has an important role in mechanisms of supraspinal, spinal, and peripheral analgesia; reward-mediating food intake and drug addiction; and modulation of emotion and stress responses. Endogenous opioids may participate in the pathophysiology of Parkinson disease (PD) and seizures, and may have an important role in mechanisms of neuroprotection. All these subjects have been recently reviewed.1,–,11 ### Endogenous opioids. The endogenous opioids consist of 3 families that derive from proteolytic cleavage of large protein precursors. These include proopiomelanocortin (POMC), which is the precursor of β-endorphin; preproenkephalin (PENK), which is the precursor of leucine (Leu)- and methionine (Met)-enkephalins; and preprodynorphin (PDYN), which is the precursor of dynorphins (including dynorphins A and B, and neoendorphins).4,5,8 Two additional endogenous opioid peptides, endomorphin-1 and -2, have been identified, but their function is still incompletely understood. All opioid peptides share a common amino (N)-terminal signature tetrapeptide sequence Tyr (tyrosine)-Gly (glycine)-Gly-Phe (phenylalanine), which interacts with the 3 types of opioid receptors. Nociceptin (previously referred to as orphanin FQ) is produced by the precursor pronociceptin (PNOC); it lacks the N-terminal …