HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 21, 18776-18784, May 23, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/21/18776    most recent M300525200v1 Alert me when this article is cited 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Borgland, S. L. Articles by Christie, M. J. Search for Related Content PubMed PubMed Citation Articles by Borgland, S. L. Articles by Christie, M. J. Social Bookmarking                      What's this?

Opioid Agonists Have Different Efficacy Profiles for G Protein Activation, Rapid Desensitization, and Endocytosis of Mu-opioid Receptors^*

Stephanie L. Borgland , Mark Connor  , Peregrine B. Osborne ¶ ||, John B. Furness ** and MacDonald J. Christie   ¶¶

From the Department of Pharmacology, The University of Sydney, New South Wales 2006, Medical Foundation, The University of Sydney, New South Wales 2006, Pain Management Research Institute, The University of Sydney, New South Wales 2006, ^¶ Prince of Wales Medical Research Institute, University of New South Wales, Randwick, New South Wales 2031, ^** Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia

The differential ability of various µ-opioid receptor (MOP) agonists to induce rapid receptor desensitization and endocytosis of MOP could arise simply from differences in their efficacy to activate G proteins or, alternatively, be due to differential capacity for activation of other signaling processes. We used AtT20 cells stably expressing a low density of FLAG-tagged MOP to compare the efficacies of a range of agonists to 1) activate G proteins using inhibition of calcium channel currents (I_Ca) as a reporter before and after inactivation of a fraction of receptors by -chlornaltrexamine, 2) produce rapid, homologous desensitization of I_Ca inhibition, and 3) internalize receptors. Relative efficacies determined for G protein coupling were [Tyr-D-Ala-Gly-MePhe-Glyol]enkephalin (DAMGO) (1) > methadone (0.98) > morphine (0.58) > pentazocine (0.15). The same rank order of efficacies for rapid desensitization of MOP was observed, but greater concentrations of agonist were required than for G protein activation. By contrast, relative efficacies for promoting endocytosis of MOP were DAMGO (1) > methadone (0.59) >> morphine (0.07) > pentazocine (0.03). These results indicate that the efficacy of opioids to produce activation of G proteins and rapid desensitization is distinct from their capacity to internalize µ-opioid receptors but that, contrary to some previous reports, morphine can produce rapid, homologous desensitization of MOP.

Received for publication, January 16, 2003 , and in revised form, March 5, 2003.

Supported by National Health & Medical Research Council of Australia Project Grant 153911. To whom correspondence should be addressed: Dept. of Pharmacology, D06, University of Sydney, Sydney, NSW 2006, Australia. Tel.: 612-9351-2408; Fax: 612-9351-3868; E-mail: markc{at}pharmacol.usyd.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Arttamangkul, N. Quillinan, M. J. Low, M. von Zastrow, J. Pintar, and J. T. Williams Differential Activation and Trafficking of {micro}-Opioid Receptors in Brain Slices Mol. Pharmacol., October 1, 2008; 74(4): 972 - 979. [Abstract] [Full Text] [PDF]

				Z.-Y. Hu, P.-T. Lin, J. Liu, and D.-Q. Liao Remifentanil induces L-type Ca2+ channel inhibition in human mesenteric arterial smooth muscle cells: [Le remifentanil provoque l'inhibition des canaux calciques de type L dans les cellules musculaires lisses des arteres mesenteriques chez l'humain] Can J Anesth, April 1, 2008; 55(4): 238 - 244. [Abstract] [Full Text] [PDF]

				M. S. Virk and J. T. Williams Agonist-Specific Regulation of {micro}-Opioid Receptor Desensitization and Recovery from Desensitization Mol. Pharmacol., April 1, 2008; 73(4): 1301 - 1308. [Abstract] [Full Text] [PDF]

				M. M. Hammer, T. S. Wehrman, and H. M. Blau A novel enzyme complementation-based assay for monitoring G-protein-coupled receptor internalization FASEB J, December 1, 2007; 21(14): 3827 - 3834. [Abstract] [Full Text] [PDF]

				K. A. Berg, A. M. Patwardhan, T. A. Sanchez, Y. M. Silva, K. M. Hargreaves, and W. P. Clarke Rapid Modulation of {micro}-Opioid Receptor Signaling in Primary Sensory Neurons J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 839 - 847. [Abstract] [Full Text] [PDF]

				E. Navratilova, S. Waite, D. Stropova, M. C. Eaton, I. D. Alves, V. J. Hruby, W. R. Roeske, H. I. Yamamura, and E. V. Varga Quantitative Evaluation of Human {delta} Opioid Receptor Desensitization Using the Operational Model of Drug Action Mol. Pharmacol., May 1, 2007; 71(5): 1416 - 1426. [Abstract] [Full Text] [PDF]

				E. A. Johnson, S. Oldfield, E. Braksator, A. Gonzalez-Cuello, D. Couch, K. J. Hall, S. J. Mundell, C. P. Bailey, E. Kelly, and G. Henderson Agonist-Selective Mechanisms of {micro}-Opioid Receptor Desensitization in Human Embryonic Kidney 293 Cells Mol. Pharmacol., August 1, 2006; 70(2): 676 - 685. [Abstract] [Full Text] [PDF]

				M. J. Clark, C. A. Furman, T. D. Gilson, and J. R. Traynor Comparison of the Relative Efficacy and Potency of {micro}-Opioid Agonists to Activate G{alpha}i/o Proteins Containing a Pertussis Toxin-Insensitive Mutation J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 858 - 864. [Abstract] [Full Text] [PDF]

				S. Arttamangkul, M. Torrecilla, K. Kobayashi, H. Okano, and J. T. Williams Separation of {micro}-Opioid Receptor Desensitization and Internalization: Endogenous Receptors in Primary Neuronal Cultures J. Neurosci., April 12, 2006; 26(15): 4118 - 4125. [Abstract] [Full Text] [PDF]

				V. C. Dang and J. T. Williams Morphine-Induced {micro}-Opioid Receptor Desensitization Mol. Pharmacol., October 1, 2005; 68(4): 1127 - 1132. [Abstract] [Full Text] [PDF]

				Z. Zuo The Role of Opioid Receptor Internalization and {beta}-Arrestins in the Development of Opioid Tolerance Anesth. Analg., September 1, 2005; 101(3): 728 - 734. [Abstract] [Full Text] [PDF]

				Q. Liu, R. Cescato, D. A. Dewi, J. Rivier, J.-C. Reubi, and A. Schonbrunn Receptor Signaling and Endocytosis Are Differentially Regulated by Somatostatin Analogs Mol. Pharmacol., July 1, 2005; 68(1): 90 - 101. [Abstract] [Full Text] [PDF]

				L. Thielemans, I. Depoortere, J. Perret, P. Robberecht, Y. Liu, T. Thijs, C. Carreras, E. Burgeon, and T. L. Peeters Desensitization of the Human Motilin Receptor by Motilides J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1397 - 1405. [Abstract] [Full Text] [PDF]

				J. K. Melichar, S. P. Hume, T. M. Williams, M. R. C. Daglish, L. G. Taylor, R. Ahmad, A. L. Malizia, D. J. Brooks, J. S. Myles, A. Lingford-Hughes, et al. Using [11C]Diprenorphine to Image Opioid Receptor Occupancy by Methadone in Opioid Addiction: Clinical and Preclinical Studies J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 309 - 315. [Abstract] [Full Text] [PDF]

				T. Koch, A. Widera, K. Bartzsch, S. Schulz, L.-O. Brandenburg, N. Wundrack, A. Beyer, G. Grecksch, and V. Hollt Receptor Endocytosis Counteracts the Development of Opioid Tolerance Mol. Pharmacol., January 1, 2005; 67(1): 280 - 287. [Abstract] [Full Text] [PDF]

				C. P. Bailey, E. Kelly, and G. Henderson Protein Kinase C Activation Enhances Morphine-Induced Rapid Desensitization of {micro}-Opioid Receptors in Mature Rat Locus Ceruleus Neurons Mol. Pharmacol., December 1, 2004; 66(6): 1592 - 1598. [Abstract] [Full Text] [PDF]

				V. C. Dang and J. T. Williams Chronic Morphine Treatment Reduces Recovery from Opioid Desensitization J. Neurosci., September 1, 2004; 24(35): 7699 - 7706. [Abstract] [Full Text] [PDF]

				B. M. Cox and A. T. Crowder Receptor Domains Regulating {micro} Opioid Receptor Uncoupling and Internalization: Relevance to Opioid Tolerance Mol. Pharmacol., March 1, 2004; 65(3): 492 - 495. [Full Text] [PDF]

				J. Celver, M. Xu, W. Jin, J. Lowe, and C. Chavkin Distinct Domains of the {micro}-Opioid Receptor Control Uncoupling and Internalization Mol. Pharmacol., March 1, 2004; 65(3): 528 - 537. [Abstract] [Full Text] [PDF]

				T. M. Tran, J. Friedman, E. Qunaibi, F. Baameur, R. H. Moore, and R. B. Clark Characterization of Agonist Stimulation of cAMP-Dependent Protein Kinase and G Protein-Coupled Receptor Kinase Phosphorylation of the {beta}2-Adrenergic Receptor Using Phosphoserine-Specific Antibodies Mol. Pharmacol., January 1, 2004; 65(1): 196 - 206. [Abstract] [Full Text] [PDF]

				C. P. Bailey, D. Couch, E. Johnson, K. Griffiths, E. Kelly, and G. Henderson {micro}-Opioid Receptor Desensitization in Mature Rat Neurons: Lack of Interaction between DAMGO and Morphine J. Neurosci., November 19, 2003; 23(33): 10515 - 10520. [Abstract] [Full Text] [PDF]

				M. Tan, M. Groszer, A. M. Tan, A. Pandya, X. Liu, and C.-W. Xie Phosphoinositide 3-Kinase Cascade Facilitates {micro}-Opioid Desensitization in Sensory Neurons by Altering G-Protein-Effector Interactions J. Neurosci., November 12, 2003; 23(32): 10292 - 10301. [Abstract] [Full Text] [PDF]