μ-opioid receptors: Ligand-dependent activation of potassium conductance, desensitization, and internalization

Veronica A. Alvarez, Seksiri Arttamangkul, Vu Dang, Abdallah Salem, Jennifer Whistler, Mark Von Zastrow, David K. Grandy, John T. Williams

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

μ-Opioid receptor (MOR) desensitization and endocytosis have been implicated in tolerance and dependence to opioids. The efficiency of each process is known to be agonist dependent; however, it is not known what determines the relative efficiency of various agonists at either process. In the present study, homologous MOR desensitization in locus ceruleus (LC) neurons and MOR internalization in HEK293 cells were examined using a series of agonists. The results show that the rank order of this series of agonists was different when comparing the magnitude of hyperpolarization and the ability to cause desensitization in LC neurons. Endocytosis of MOR was also examined in HEK293 cells using the same agonists. The relative ability to cause endocytosis in HEK293 cells correlated with the degree of desensitization in LC cells. This strong correlation suggests that the two processes are closely linked. The results also suggest that agonist efficacy is not necessarily a predictor of the ability to cause MOR desensitization or endocytosis. Identification and characterization of the biophysical properties of agonists that favor desensitization and internalization of receptors will lead to a better understanding of opioid signaling.

Original languageEnglish (US)
Pages (from-to)5769-5776
Number of pages8
JournalJournal of Neuroscience
Volume22
Issue number13
StatePublished - Jul 1 2002
Externally publishedYes

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Keywords

  • Electrophysiology
  • Endocytosis
  • Homologous desensitization
  • Imaging
  • Locus ceruleus
  • Opioids

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Alvarez, V. A., Arttamangkul, S., Dang, V., Salem, A., Whistler, J., Von Zastrow, M., Grandy, D. K., & Williams, J. T. (2002). μ-opioid receptors: Ligand-dependent activation of potassium conductance, desensitization, and internalization. Journal of Neuroscience, 22(13), 5769-5776.