ArticleThe Journal of biological chemistry2013
Agonist-biased trafficking of somatostatin receptor 2A in enteric neurons.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology.Pharmaceutics · 2026Review
- Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Compartment-specific opioid receptor signaling is selectively modulated by different dynorphin peptides.eLife · 2021Article
- The Interplay of Glucagon-Like Peptide-1 Receptor Trafficking and Signalling in Pancreatic Beta Cells.Frontiers in endocrinology · 2021Review
- Ligand-Specific Factors Influencing GLP-1 Receptor Post-Endocytic Trafficking and Degradation in Pancreatic Beta Cells.International journal of molecular sciences · 2020Article
- Biased signaling by endogenous opioid peptides.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Combination treatments to enhance peptide receptor radionuclide therapy of neuroendocrine tumours.European journal of nuclear medicine and molecular imaging · 2020Review
- Regulated resurfacing of a somatostatin receptor storage compartment fine-tunes pituitary secretion.The Journal of cell biology · 2020Article
- 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
- Therapeutic Targeting of Endosomal G-Protein-Coupled Receptors.Trends in pharmacological sciences · 2018Review
- International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.Pharmacological reviews · 2018Review
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.American journal of physiology. Gastrointestinal and liver physiology · 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
- 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
- Visualizing and quantitating sequence-dependent GPCR recycling.Methods in cell biology · 2015Article
- Endothelin-converting enzyme 2 differentially regulates opioid receptor activity.British journal of pharmacology · 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
- Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity.Frontiers in pharmacology · 2014Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions.
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