ArticleThe Journal of physiology2011
Endothelin-converting enzyme-1 regulates trafficking and signalling of the neurokinin 1 receptor in endosomes of myenteric neurones.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Broadening the View: Substance P and Its Metabolism in Pruritus-Related Diseases.The Journal of dermatology · 2026Review
- Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway.International journal of biological sciences · 2024Article
- Susceptibility ofFrontiers in pediatrics · 2022Article
- A Novel Mechanism of Endoplasmic Reticulum Stress- and c-Myc-Degradation-Mediated Therapeutic Benefits of Antineurokinin-1 Receptor Drugs in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Neurokinin receptors and their implications in various autoimmune diseases.Current research in immunology · 2021Review
- G-Protein-Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases.Gastroenterology · 2019Review
- Inflammation-associated changes in DOR expression and function in the mouse colon.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Neuropeptide substance P and the immune response.Cellular and molecular life sciences : CMLS · 2016Review
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Protein Kinase D and Gβγ Subunits Mediate Agonist-evoked Translocation of Protease-activated Receptor-2 from the Golgi Apparatus to the Plasma Membrane.The Journal of biological chemistry · 2016Article
- G Protein-Coupled Receptor Trafficking and Signalling in the Enteric Nervous System: The Past, Present and Future.Advances in experimental medicine and biology · 2016Review
- Single Molecule Imaging Deciphers the Relation between Mobility and Signaling of a Prototypical G Protein-coupled Receptor in Living Cells.The Journal of biological chemistry · 2015Article
- Inflammation-induced abnormalities in the subcellular localization and trafficking of the neurokinin 1 receptor in the enteric nervous system.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Substance P stimulates endothelin 1 secretion via endothelin-converting enzyme 1 and promotes melanogenesis in human melanocytes.The Journal of investigative dermatology · 2015Article
- Endothelin-converting enzyme 1 and β-arrestins exert spatiotemporal control of substance P-induced inflammatory signals.The Journal of biological chemistry · 2014Article
- Opioid receptor function is regulated by post-endocytic peptide processing.The Journal of biological chemistry · 2014Article
- Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus.The Journal of clinical investigation · 2014Article
- Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease.Physiological reviews · 2014Review
- Agonist-biased trafficking of somatostatin receptor 2A in enteric neurons.The Journal of biological chemistry · 2013Article
- Roles of proteolysis in regulation of GPCR function.British journal of pharmacology · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Neuropeptide signalling at the plasma membrane is terminated by neuropeptide degradation by cell-surface peptidases, and by β-arrestin-dependent receptor desensitization and endocytosis. However, receptors continue to signal from endosomes by β-arrestin-dependent processes, and endosomal sorting mediates recycling and resensitization of plasma membrane signalling. The mechanisms that control signalling and trafficking of receptors in endosomes are poorly defined. We report a major role for endothelin-converting enzyme-1 (ECE-1) in controlling substance P (SP) and the neurokinin 1 receptor (NK(1)R) in endosomes of myenteric neurones. ECE-1 mRNA and protein were expressed by myenteric neurones of rat and mouse intestine. SP (10 nM, 10 min) induced interaction of NK(1)R and β-arrestin at the plasma membrane, and the SP-NK(1)R-β-arrestin signalosome complex trafficked by a dynamin-mediated mechanism to ECE-1-containing early endosomes, where ECE-1 can degrade SP. After 120 min, NK(1)R recycled from endosomes to the plasma membrane. ECE-1 inhibitors (SM-19712, PD-069185) and the vacuolar H(+)ATPase inhibitor bafilomycin A(1), which prevent endosomal SP degradation, suppressed NK(1)R recycling by >50%. Preincubation of neurones with SP (10 nM, 5 min) desensitized Ca(2+) transients to a second SP challenge after 10 min, and SP signals resensitized after 60 min. SM-19712 inhibited NK(1)R resensitization by >90%. ECE-1 inhibitors also caused sustained SP-induced activation of extracellular signal-regulated kinases, consistent with stabilization of the SP-NK(1)R-β-arrestin signalosome. By degrading SP and destabilizing endosomal signalosomes, ECE-1 has a dual role in controlling endocytic signalling and trafficking of the NK(1)R: promoting resensitization of G protein-mediated plasma membrane signalling, and terminating β-arrestin-mediated endosomal signalling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.