Opioid receptors signaling network

Abstract

Opioid receptors belong to the class A G‐protein‐coupled receptors and are activated by alkaloid opiates such as morphine, and endogenous ligands such as endorphins and enkephalins. Opioid receptors are widely distributed in the human body and are involved in numerous physiological processes through three major classical opioid receptor subtypes; the mu, delta and kappa along with a lesser characterized subtype, opioid receptor‐like (ORL1). Opioids are the most potent analgesics and have been extensively used as a therapeutic drug for the treatment of pain and related disorders. Chronic administration of clinically used opioids is associated with adverse effects such as drug tolerance, addiction and constipation. Several investigations attempted to identify the molecular signaling networks associated with endogenous as well as synthetic opiates, however, there is a paucity of a cumulative depiction of these signaling events. Here, we report a systemic collection of downstream molecules pertaining to four subtypes of opioid receptors (MOR, KOR, DOR and ORL1) in the form of a signaling pathway map. We manually curated reactions induced by the activation of opioid receptors from the literature into five categories‐ molecular association, activation/inhibition, catalysis, transport, and gene regulation. This led to a dataset of 180 molecules, which is collectively represented in the opioid receptor signaling network following NetPath criteria. We believe that the public availability of an opioid receptor signaling pathway map can accelerate biomedical research in this area because of its high therapeutic significance. The opioid receptors signaling pathway map is uploaded to a freely available web resource, WikiPathways enabling ease of access (https://www.wikipathways.org/index.php/Pathway:WP5093).

Transcriptomes of Clusterin- and S100B-transfected neuronal cells elucidate protective mechanisms against hypoxia and oxidative stress in the hooded seal (Cystophora cristata) brain

“…In the S100B-transfected cells neurotransmitter release might be reduced by activation of opioid signaling (z = 1.2, − log(p) = 2.1) (Fig. 10 ), which can prevent calcium ion influx and facilitate potassium ion efflux, thereby causing membrane hyperpolarization and a reduced neurotransmitter release [ 33 ]. The upregulated OPRD1 (log2FC = 0.80) may have facilitated clearance of neurotransmitters from the synaptic cleft and prevent neuroexcitotoxicity [ 37 ].…”

Epigenome-wide DNA methylation profiling of conditioned pain modulation in individuals with non-specific chronic low back pain

“…Accumulating evidence also suggests that DNA methylation of genes in MAPK signaling pathways alter inflammatory cytokine levels [ 57 ] and inhibition of MAPK decreases the expression of GABA receptors [ 53 ]. Moreover, MAPK-Ras signaling pathways have been shown to play a role in signal transduction following the activation of opioid receptors [ 54 ]. As a result, targeting this pathway has been suggested to treat painful conditions, including degenerative disc disease [ 52 , 55 ].…”

Striatal µ-Opioid Receptor Activation Triggers Direct-Pathway GABAergic Plasticity to Induce Negative Affect

“…The addictive properties of opioids are mediated by MORs, and MOR activation is known to inhibit neuronal activity in the hippocampus and ventral tegmental area ( Al-Hasani and Bruchas, 2011 ; Evans, 2004 ; Gaveriaux-Ruff and Kieffer, 2002 ; Gopalakrishnan et al, 2021 ; Volkow et al, 2019 ; Williams et al, 2001 ; Williams et al, 2013 ). Our study found that acute MOR activation inhibited GABAergic dMSN◊EP/GPh transmission.…”