QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 11, 2009, 29(10):3322-3327; doi:10.1523/JNEUROSCI.4749-08.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dang, V. C. Articles by Christie, M. J. Search for Related Content PubMed PubMed Citation Articles by Dang, V. C. Articles by Christie, M. J.

 Previous Article  |  Next Article 

Brief Communications
Two Distinct Mechanisms Mediate Acute µ-Opioid Receptor Desensitization in Native Neurons

Vu C. Dang,¹ Ian A. Napier,^1,2 and MacDonald J. Christie^1,2

¹Pain Management Research Institute and ²Brain and Mind Research Institute, The University of Sydney, New South Wales 2006, Australia

Correspondence should be addressed to MacDonald J. Christie, Brain and Mind Research Institute, M02G, The University of Sydney, NSW 2006, Australia. Email: macc{at}med.usyd.edu.au

Sustained stimulation of G-protein coupled receptors (GPCRs) leads to rapid loss of receptor function (acute desensitization). For many GPCRs including the µ-opioid receptor (MOR), an accepted mechanism for acute desensitization is through G-protein coupled receptor kinase (GRKs) mediated phosphorylation of the receptor, which facilitates the binding of β-arrestins (βarrs) to the receptor and then promotes endocytosis. However, the mechanism(s) that mediate acute desensitization have not yet been well defined in native neurons. This study used whole-cell patch clamp recording of G-protein coupled inward-rectifying potassium (GIRK) currents to assay MOR function and identify mechanisms of acute MOR desensitization in locus ceruleus (LC) neurons. The rate and extent of MOR desensitization were unaffected by βarr-2 knock-out. Disruption of GRK2 function via inhibitory peptide introduced directly into neurons also failed to affect desensitization in wild type or βarr-2 knock-outs. Inhibition of ERK1/2 activation alone had little effect on acute desensitization. However, when both GRK2-βarr-2 and ERK1/2 functions were disrupted simultaneously, desensitization of MOR was nearly abolished. Together, these results suggest that acute desensitization of MOR in native LC neurons is determined by at least two molecular pathways, one involving GRK2 and βarr-2, and a parallel pathway mediated by activated ERK1/2.

---

Received Oct. 3, 2008; revised Jan. 29, 2009; accepted Feb. 15, 2009.

Correspondence should be addressed to MacDonald J. Christie, Brain and Mind Research Institute, M02G, The University of Sydney, NSW 2006, Australia. Email: macc{at}med.usyd.edu.au

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help