Desensitization and trafficking of μ-opioid receptors in locus ceruleus neurons: Modulation by kinases

Seksiri Arttamangkul, Elaine K. Lau, Hsin Wei Lu, John Williams

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The phosphorylation of μ-opioid receptors (MOPRs) by G protein-coupled receptor kinases (GRKs), followed by arrestin binding, is thought to be a key pathway leading to desensitization and internalization. The present study used the combination of intracellular and whole-cell recordings from rats and mice, as well as live cell imaging of Flag-tagged MOPRs from mouse locus ceruleus neurons, to examine the role of protein kinases in acute desensitization and receptor trafficking. Inhibition of GRKs by using heparin or GRK2-mutant mice did not block desensitization or alter the rate of recovery from desensitization. The nonselective kinase inhibitor staurosporine did not reduce the extent of [Met 5]enkephalin (ME)-induced desensitization but increased the rate of recovery from desensitization. In the presence of staurosporine, ME-activated FlagMOPRs were internalized but did not traffic away from the plasma membrane. The increased rate of recovery from desensitization correlated with the enhancement in the recycling of receptors to the plasma membrane. ME-induced MOPR desensitization persisted and the trafficking of receptors was modified after inhibition of protein kinases. The results suggest that desensitization of MOPRs may be an early step after agonist binding that is modulated by but is not dependent on kinase activity.

Original languageEnglish (US)
Pages (from-to)348-355
Number of pages8
JournalMolecular Pharmacology
Volume81
Issue number3
DOIs
StatePublished - Mar 2012

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Methionine Enkephalin
Locus Coeruleus
Opioid Receptors
G-Protein-Coupled Receptor Kinases
Phosphotransferases
Staurosporine
Neurons
Protein Kinases
Cell Membrane
Arrestin
Patch-Clamp Techniques
Heparin
Phosphorylation

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Desensitization and trafficking of μ-opioid receptors in locus ceruleus neurons : Modulation by kinases. / Arttamangkul, Seksiri; Lau, Elaine K.; Lu, Hsin Wei; Williams, John.

In: Molecular Pharmacology, Vol. 81, No. 3, 03.2012, p. 348-355.

Research output: Contribution to journalArticle

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