{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe nociceptin/orphanin FQ receptor, encoded by the OPRL1 gene, exhibits unique structural and signaling properties that distinguish it from classical opioid receptors. High‐resolution structural studies have revealed ligand–receptor contacts and divergent pocket conformations that underlie its selective binding to nociceptin‐related peptides (e.g., PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Detailed investigations in cultured cells have shown that receptor activation triggers rapid, clathrin‐mediated internalization and recycling, processes critically dependent on C-terminal phosphorylation (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Complementary mapping studies and mutagenesis further delineated the ligand‐bound conformations and key cysteine residues within the transmembrane domains that contribute to binding and dimerization with other G protein‐coupled receptors, thus modulating G protein engagement and biased signaling (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, studies in heterologous systems have confirmed that OPRL1 efficiently couples to inhibitory G proteins and undergoes desensitization dynamics similar to other opioid receptors (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOPRL1 plays a pivotal role in the modulation of stress, fear, addiction, and affective processes. Experimental work in animal models demonstrates that receptor activation within amygdalar circuits impairs fear memory consolidation, suggesting a protective “brake” mechanism against posttraumatic stress disorder (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Genetic and epigenetic association studies have linked OPRL1 variants and promoter methylation changes to increased vulnerability to alcohol dependence and other substance use disorders, while the downregulation of its endogenous ligand system in key limbic regions may underlie deficits in cognitive control observed in alcoholism (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In humans, neuroimaging and allelic studies further implicate this receptor in stress resilience and suicide risk, and methylation analyses support its involvement in stress‐related alcohol use (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", and PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond central effects, OPRL1 is expressed in peripheral tissues where it contributes to immune regulation and vascular functions. Mapping studies in human trigeminal ganglia have identified robust nociceptin immunoreactivity and OPRL1 mRNA colocalizing with neuropeptides involved in nociception (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " In immune cells, activation of the receptor modulates chemokine production and cross‐desensitizes other chemotactic receptors, thereby influencing inflammatory responses (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "and PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " Consistent with these findings, expression on leukocyte subsets has been linked to altered cytokine output, and cross-talk with receptors such as CXCR4 may reduce susceptibility to viral infection (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "and PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " In addition, expression in endothelial cells and skin has been associated with MAP kinase activation and modulation of neuropathic pain symptoms, underscoring the receptor’s role in vascular homeostasis (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "and PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": ", while altered plasma levels of nociceptin have been observed in acute cardiovascular disease (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional research highlights the involvement of OPRL1 in neural repair and reproductive functions. For instance, interactions with neurite growth regulators can modulate axonal glycosylation and surface expression, thereby influencing neural regeneration following traumatic injury (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": " Genetic variants of OPRL1 have also been implicated in individual differences in vulnerability to opiate addiction (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": " Moreover, within hypothalamic circuits, OPRL1 modulates reproductive behavior via regulation of β-endorphin neuronal activity, contributing to ovarian hormone feedback loops (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": " Finally, cross-talk with glutamatergic systems, as demonstrated by kainate-induced downregulation of receptor mRNA, further attests to the complex interplay of excitatory and inhibitory signals mediated by OPRL1 (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aaron A Thompson, Wei Liu, Eugene Chun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11085"}], "href": "https://doi.org/10.1038/nature11085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22596163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22596163"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maithé Corbani, Christophe Gonindard, Jean-Claude Meunier "}, {"type": "b", "children": [{"type": "t", "text": "Ligand-regulated internalization of the opioid receptor-like 1: a confocal study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2004-0062"}], "href": "https://doi.org/10.1210/en.2004-0062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15016723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15016723"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nancy R Zhang, William Planer, Edward R Siuda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine 363 is required for nociceptin/orphanin FQ opioid receptor (NOPR) desensitization, internalization, and arrestin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.405696"}], "href": "https://doi.org/10.1074/jbc.M112.405696"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23086955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23086955"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "S Spampinato, R Di Toro, M Alessandri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Agonist-induced internalization and desensitization of the human nociceptin receptor expressed in CHO cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s000180200016"}], "href": "https://doi.org/10.1007/s000180200016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12568343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12568343"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Natsuyo Akuzawa, Shigeki Takeda, Masaji Ishiguro "}, {"type": "b", "children": [{"type": "t", "text": "Structural modelling and mutation analysis of a nociceptin receptor and its ligand complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvm100"}], "href": "https://doi.org/10.1093/jb/mvm100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17456499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17456499"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ayami Matsushima, Hirokazu Nishimura, Yutaka Matsuyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific affinity-labeling of the nociceptin ORL1 receptor using a thiol-activated Cys(Npys)-containing peptide ligand."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biopolymers (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bip.22792"}], "href": "https://doi.org/10.1002/bip.22792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27271345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27271345"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jing Chen, Zhengwen Wang, Rumin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterodimerization of apelin and opioid receptor-like 1 receptors mediates apelin-13-induced G protein biased signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2023.121892"}], "href": "https://doi.org/10.1016/j.lfs.2023.121892"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37364634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37364634"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Prudence H Tso, Yung H Wong "}, {"type": "b", "children": [{"type": "t", "text": "Opioid receptor-like (ORL1) receptor utilizes both G(oA) and G(oB) for signal transduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Pept Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/092986606776819547"}], "href": "https://doi.org/10.2174/092986606776819547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16800795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16800795"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Raül Andero, Shaun P Brothers, Tanja Jovanovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Transl Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scitranslmed.3005656"}], "href": "https://doi.org/10.1126/scitranslmed.3005656"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23740899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23740899"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Alexander Kuzmin, Igor Bazov, Donna Sheedy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of pronociceptin and its receptor is downregulated in the brain of human alcoholics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2009.05.067"}], "href": "https://doi.org/10.1016/j.brainres.2009.05.067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19501074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19501074"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jia Huang, Brandon Young, Mathew T Pletcher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between the nociceptin receptor gene (OPRL1) single nucleotide polymorphisms and alcohol dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Addict Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1369-1600.2007.00089.x"}], "href": "https://doi.org/10.1111/j.1369-1600.2007.00089.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18269382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18269382"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xiaoling Xuei, Leah Flury-Wetherill, Laura Almasy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association analysis of genes encoding the nociceptin receptor (OPRL1) and its endogenous ligand (PNOC) with alcohol or illicit drug dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Addict Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1369-1600.2007.00082.x"}], "href": "https://doi.org/10.1111/j.1369-1600.2007.00082.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17910740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17910740"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Rajesh Narendran, Savannah Tollefson, Kelli Fasenmyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence: Therapeutic Implications for Posttraumatic Stress Disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2019.02.017"}], "href": "https://doi.org/10.1016/j.biopsych.2019.02.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30954231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30954231"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Pierre-Eric Lutz, Yi Zhou, Aurélie Labbe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Neuropsychopharmacol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.euroneuro.2015.08.015"}], "href": "https://doi.org/10.1016/j.euroneuro.2015.08.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26349406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26349406"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Barbara Ruggeri, Christine Macare, Serena Stopponi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Child Psychol Psychiatry (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcpp.12843"}], "href": "https://doi.org/10.1111/jcpp.12843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29197086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29197086"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Allison Jane Fulford "}, {"type": "b", "children": [{"type": "t", "text": "Endogenous nociceptin system involvement in stress responses and anxiety behavior."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vitam Horm (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/bs.vh.2014.12.012"}], "href": "https://doi.org/10.1016/bs.vh.2014.12.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25677776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25677776"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Xinmin Simon Xie "}, {"type": "b", "children": [{"type": "t", "text": "The neuronal circuit between nociceptin/orphanin FQ and hypocretins/orexins coordinately modulates stress-induced analgesia and anxiety-related behavior."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vitam Horm (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/bs.vh.2014.11.004"}], "href": "https://doi.org/10.1016/bs.vh.2014.11.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25677777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25677777"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Mingyan Hou, Rolf Uddman, Janos Tajti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nociceptin immunoreactivity and receptor mRNA in the human trigeminal ganglion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-8993(02)03927-6"}], "href": "https://doi.org/10.1016/s0006-8993(02"}, {"type": "t", "text": "03927-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12576178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12576178"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Elaine C Gavioli, Iris Ucella de Medeiros, Marta C Monteiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nociceptin/orphanin FQ-NOP receptor system in inflammatory and immune-mediated diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vitam Horm (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/bs.vh.2014.11.003"}], "href": "https://doi.org/10.1016/bs.vh.2014.11.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25677775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25677775"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "David E Kaminsky, Thomas J Rogers "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of CCL2/MCP-1 and CCL5/RANTES expression by nociceptin in human monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuroimmune Pharmacol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11481-007-9086-y"}], "href": "https://doi.org/10.1007/s11481-007-9086-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18247127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18247127"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "C Krüger, L Köthe, A Struppert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Expression und function of the ORL-1 receptor on human leukocytes]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Schmerz (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00482-006-0488-1"}], "href": "https://doi.org/10.1007/s00482-006-0488-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16807742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16807742"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "David E Kaminsky, Thomas J Rogers "}, {"type": "b", "children": [{"type": "t", "text": "Nociceptin/orphanin FQ receptor-driven heterologous desensitization of the major HIV-1 co-receptor CXCR4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuroimmune Pharmacol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11481-011-9285-4"}], "href": "https://doi.org/10.1007/s11481-011-9285-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21656184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21656184"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Filippo Granata, Rossella Luisa Potenza, Anna Fiori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of OP4 (ORL1, NOP1) receptors in vascular endothelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2003.09.049"}], "href": "https://doi.org/10.1016/j.ejphar.2003.09.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14660000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14660000"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Baohan Pan, Wolfgang Schröder, Ruth Jostock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nociceptin/orphanin FQ opioid peptide-receptor expression in pachyonychia congenita."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Peripher Nerv Syst (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jns.12288"}], "href": "https://doi.org/10.1111/jns.12288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30255608"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30255608"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Cs Csobay-Novák, P Sótonyi, M Krepuska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Physiol Hung (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1556/APhysiol.99.2012.2.2"}], "href": "https://doi.org/10.1556/APhysiol.99.2012.2.2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22849833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22849833"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yuichi Sekine, Chad S Siegel, Tomoko Sekine-Konno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aao4180"}], "href": "https://doi.org/10.1126/scisignal.aao4180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29615517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29615517"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Judith A Briant, David A Nielsen, Dmitri Proudnikov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for association of two variants of the nociceptin/orphanin FQ receptor gene OPRL1 with vulnerability to develop opiate addiction in Caucasians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Psychiatr Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/YPG.0b013e32833511f6"}], "href": "https://doi.org/10.1097/YPG.0b013e32833511f6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20032820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20032820"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Kevin Sinchak, Lauren Dalhousay, Nayna Sanathara "}, {"type": "b", "children": [{"type": "t", "text": "Orphanin FQ-ORL-1 regulation of reproduction and reproductive behavior in the female."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vitam Horm (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/bs.vh.2014.11.002"}], "href": "https://doi.org/10.1016/bs.vh.2014.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25677773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25677773"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Rosalia Cannarsa, Daniela Landuzzi, Chiara Cavina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kainic acid down-regulates NOP receptor density and gene expression in human neuroblastoma SH-SY5Y cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-008-9038-x"}], "href": "https://doi.org/10.1007/s12031-008-9038-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18286384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18286384"}]}]}]}