Nociceptin-induced internalization of the ORL1 receptor in human neuroblastoma cells

Spampinato, Santi; Toro, Rosanna Di; Qasem, Ahmad

doi:10.1097/00001756-200110080-00035

Cited by 36 publications

(44 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CCR7 GPCR, like the nociceptin GPCR demonstrates ligand-dependent differences in receptor internalization and desensitization (57)(58)(59)(60). Both GPCRs differentially regulate receptor fate following ligand binding (45).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Arrestin 3 Mediates Endocytosis of CCR7 following Ligation of CCL19 but Not CCL21

Byers

Calloway

Shannon

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Internalization of ligand bound G protein-coupled receptors, an important cellular function that mediates receptor desensitization, takes place via distinct pathways, which are often unique for each receptor. The C-C chemokine receptor (CCR7) G protein-coupled receptor is expressed on naive T cells, dendritic cells, and NK cells and has two endogenous ligands, CCL19 and CCL21. Following binding of CCL21, 21 ± 4% of CCR7 is internalized in the HuT 78 human T cell lymphoma line, while 76 ± 8% of CCR7 is internalized upon binding to CCL19. To determine whether arrestins mediated differential internalization of CCR7/CCL19 vs CCR7/CCL21, we used small interfering RNA (siRNA) to knock down expression of arrestin 2 or arrestin 3 in HuT 78 cells. Independent of arrestin 2 or arrestin 3 expression, CCR7/CCL21 internalized. In contrast, following depletion of arrestin 3, CCR7/CCL19 failed to internalize. To examine the consequence of complete loss of both arrestin 2 and arrestin 3 on CCL19/CCR7 internalization, we examined CCR7 internalization in arrestin 2−/−/arrestin 3−/− murine embryonic fibroblasts. Only reconstitution with arrestin 3-GFP but not arrestin 2-GFP rescued internalization of CCR7/CCL19. Loss of arrestin 2 or arrestin 3 blocked migration to CCL19 but had no effect on migration to CCL21. Using immunofluorescence microscopy, we found that arrestins do not cluster at the membrane with CCR7 following ligand binding but cap with CCR7 during receptor internalization. These are the first studies that define a role for arrestin 3 in the internalization of a chemokine receptor following binding of one but not both endogenous ligands.

show abstract

Section: Discussionmentioning

confidence: 99%

“…2), the nociceptin receptor required different ligand-dependent incubation times to mediate receptor internalization. This may reflect the differential functions of the described ligands, since agonists and antagonists were internalized at different rates (57)(58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

Arrestin 3 Mediates Endocytosis of CCR7 following Ligation of CCL19 but Not CCL21

Byers

Calloway

Shannon

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Numerous groups have investigated the many stages of NOP receptor trafficking (for a thorough review, see Donica et al, 2013). Early work in the NOP receptor field had difficulty in finding agonistinduced internalization (Dautzenberg et al, 2001); however, later reports showed that NOP receptors indeed internalized in response to N/OFQ treatment (Spampinato et al, 2001(Spampinato et al, , 2002. Similar to the kappa opioid receptor disparities in internalization conditions , it is likely that differences reported in the internalization of NOP receptors are due to expression variability and model system used.…”

Section: B Nop Receptors and Kinase Signalingmentioning

confidence: 99%

“…Similar to the kappa opioid receptor disparities in internalization conditions , it is likely that differences reported in the internalization of NOP receptors are due to expression variability and model system used. In most cases, NOP receptors have been shown to start internalizing fairly rapidly, within 5-10 minutes after agonist treatment, with very robust internalization at 1 hour posttreatment in transfected cells (Spampinato et al, 2001;Corbani et al, 2004;Zhang et al, 2012a). As with the mu receptor, the level of internalized receptor depends on the ligand.…”

Section: B Nop Receptors and Kinase Signalingmentioning

confidence: 99%

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

View full text Add to dashboard Cite

The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor

show abstract

“…Like all other neuropeptides, the heptadecapeptid N/OFQ is synthesized as a part of a larger precursor named prepro-nociceptin, a 176 aminoacid polypeptide in human, from which N/OFQ and nocistatin are cleaved in brain cells and peripheral neurons [16,17] . Although nociceptin is present in the brain, the liquor and blood, human immune cells and polymorphonuclear cells, the gastrointestinal tract and other organs, there are no data on N/OFQ or its receptor in malignant diseases with exception of human neuroblastoma cell lines [18,19] . This is the first report focusing on nociceptin in hepatocellular carcinoma and other liver diseases.…”

Section: Discussionmentioning

confidence: 99%

Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma

Szalay¹,

Hantos²,

Horváth³

et al. 2004

WJG

View full text Add to dashboard Cite

show abstract

Nociceptin-induced internalization of the ORL1 receptor in human neuroblastoma cells

Cited by 36 publications

References 24 publications

Arrestin 3 Mediates Endocytosis of CCR7 following Ligation of CCL19 but Not CCL21

Arrestin 3 Mediates Endocytosis of CCR7 following Ligation of CCL19 but Not CCL21

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma

Contact Info

Product

Resources

About