Opioid receptor-like 1 (OPRL1) (OPRL1)

Opioid receptor-like 1 (OPRL1), also known as the nociceptin receptor (NOP), is a G protein-coupled receptor (GPCR) that belongs to the opioid receptor family but exhibits distinct pharmacological profiles compared to classical mu, delta, and kappa receptors (UniProt P41146) [1]. Its endogenous ligand is the heptadecapeptide nociceptin/orphanin FQ (N/OFQ), which modulates various physiological processes including pain perception, stress, and reward (IUPHAR/BPS Guide to Pharmacology) [2]. OPRL1 is highly expressed in the brain and spinal cord, particularly in the amygdala, hippocampus, and dorsal horn, where it regulates neurotransmitter release via Gi/o protein signaling (PubMed PMID: 30107054) [3]. In the context of pain, OPRL1 activation can produce analgesia, making it a target for novel pain medications like cebranopadol (PubMed PMID: 25637951) [4]. Additionally, OPRL1 is implicated in psychiatric conditions such as anxiety and depression, as well as neurological disorders like Parkinson's disease (PubChem CID 5485) [5]. Therapeutic strategies involve OPRL1 agonists for chronic pain and antagonists for treating mood disorders and substance abuse (PubMed PMID: 29153145) [6]. The receptor's unique role in the "anti-opioid" system also makes it a candidate for reducing the side effects and abuse potential of traditional opioids (PubMed PMID: 24050313) [7].

Other names

Nociceptin receptorORL1Nociceptin/orphanin FQ receptorNOPKappa-type opioid receptor-like 1

Agonism of the OPRL1 receptor inhibits adenylate cyclase and activates G protein-coupled inwardly rectifying potassium (GIRK) channels, leading to hyperpolarization and reduced neuronal excitability (UniProt P41146) [1]. This modulates the release of neurotransmitters like glutamate and GABA to influence pain and stress pathways (PubMed PMID: 30107054) [3].