Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia
| Autor: | Isabelle Lena, Lan Bao, Zhen Ning Zhang, Zhen-Zhong Xu, Shao Qiu He, Andreas Zimmer, Tao Sun, Li-Hua Wang, Ji-Song Guan, Guo Qiang Ma, Xu Zhang, Gang Pei, Ian Kitchen, Cheng He, Hua Gao, Robert Elde |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Pain Substance P Physical dependence Receptors Cell Surface Biology PC12 Cells Synaptic Transmission General Biochemistry Genetics and Molecular Biology Exocytosis chemistry.chemical_compound Mice Microscopy Electron Transmission Ganglia Spinal Receptors Opioid delta Tachykinins medicine Animals Neurons Afferent Protein Precursors Receptor Cells Cultured Mice Knockout Afferent Pathways Biochemistry Genetics and Molecular Biology(all) Secretory Vesicles Cell Membrane Receptor Aggregation Nociceptors Anatomy Spinal cord Cell biology Protein Structure Tertiary Rats Analgesics Opioid medicine.anatomical_structure Nociception Opioid chemistry Knockout mouse medicine.symptom Gene Deletion medicine.drug |
| Zdroj: | Cell. 122(4) |
| ISSN: | 0092-8674 |
| Popis: | SummaryOpioid and tachykinin systems are involved in modulation of pain transmission in the spinal cord. Regulation of surface opioid receptors on nociceptive afferents is critical for opioid analgesia. Plasma-membrane insertion of δ-opioid receptors (DORs) is induced by stimulus-triggered exocytosis of DOR-containing large dense-core vesicles (LDCVs), but how DORs become sorted into the regulated secretory pathway is unknown. Here we report that direct interaction between protachykinin and DOR is responsible for sorting of DORs into LDCVs, allowing stimulus-induced surface insertion of DORs and DOR-mediated spinal analgesia. This interaction is mediated by the substance P domain of protachykinin and the third luminal domain of DOR. Furthermore, deletion of the preprotachykinin A gene reduced stimulus-induced surface insertion of DORs and abolished DOR-mediated spinal analgesia and morphine tolerance. Thus, protachykinin is essential for modulation of the sensitivity of nociceptive afferents to opioids, and the opioid and tachykinin systems are directly linked by protachykinin/DOR interaction. |
| Databáze: | OpenAIRE |
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