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Morphine Activates Opioid Receptors without Causing Their Rapid Internalization
Open accessAbstract
We have examined the endocytic trafficking of epitope-tagged delta and mu opioid receptors expressed in human embryonic kidney (HEK) 293 cells. These receptors are activated by peptide agonists (enkephalins) as well as by the alkaloid agonist drugs etorphine and morphine. Enkephalins and etorphine cause opioid receptors to internalize rapidly (t1/2 approximately 6 min) by a mechanism similar to that utilized by a number of other classes of receptor, as indicated by localization of internalized opioid receptors in transferrin-containing endosomes and inhibition of opioid receptor internalization by hypertonic media. Remarkably, morphine does not stimulate the rapid internalization of either delta or mu opioid receptors, even at high concentrations that strongly inhibit adenylyl cyclase. These data indicate that agonist ligands, which have similar effects on receptor-mediated signaling, can have dramatically different effects on the intracellular trafficking of a G protein-coupled receptor.
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Cited by
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Williams, J. T., Ingram, S. L., Henderson, G., Chavkin, C., von Zastrow, M., Schulz, S., Koch, T., Evans, C. J., & Christie, M. J. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.005942 · Cited by 802
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Neptune, E. R., & Bourne, H. R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14489 · Cited by 274
Lutfy, K., Eitan, S., Bryant, C. D., Yang, Y. C., Saliminejad, N., Walwyn, W., Kieffer, B. L., Takeshima, H., Carroll, F. I., Maidment, N. T., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-32-10331.2003 · Cited by 211
Self-citationTanowitz, M., & von Zastrow, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304504200 · Cited by 169
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Metadata
- Authors
- Keith, D. E., Murray, S. R., Zaki, P. A., Chu, P. C., Lissin, D. V., Kang, L., Evans, C. J., & von Zastrow, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 271
- Issue
- 32
- Pages
- 19021-19024
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2127846911
- Cited by
- 552
- References
- 0
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Keith, D. E., Murray, S. R., Zaki, P. A., Chu, P. C., Lissin, D. V., Kang, L., Evans, C. J., & von Zastrow, M. (1996). Morphine Activates Opioid Receptors without Causing Their Rapid Internalization. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.271.32.19021
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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