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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) 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 Web of Science 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 Web of Science (58) Citing Articles via Google Scholar Google Scholar Articles by Coutts, A. A. Articles by Irving, A. J. Search for Related Content PubMed PubMed Citation Articles by Coutts, A. A. Articles by Irving, A. J.

 Previous Article  |  Next Article 

The Journal of Neuroscience, April 1, 2001, 21(7):2425-2433

Agonist-Induced Internalization and Trafficking of Cannabinoid CB₁ Receptors in Hippocampal Neurons

Angela A. Coutts¹, Sharon Anavi-Goffer¹, Ruth A. Ross¹, David J. MacEwan¹, Ken Mackie², Roger G. Pertwee¹, and Andrew J. Irving^{1, 3}

¹ Department of Biomedical Sciences, University of Aberdeen, Scotland, AB25 2ZD, United Kingdom, ² Department of Anesthesiology, University of Washington, Seattle, Washington 98195, and ³ Neurosciences Institute, Department of Pharmacology and Neuroscience, University of Dundee, Scotland, DD1 9SY, United Kingdom

Agonist-induced internalization of G-protein-coupled receptors is an important mechanism for regulating receptor abundance and availability at the plasma membrane. In this study we have used immunolabeling techniques and confocal microscopy to investigate agonist-induced internalization and trafficking of CB₁ receptors in rat cultured hippocampal neurons. The levels of cell surface CB₁ receptor immunoreactivity associated with presynaptic GABAergic terminals decreased markedly (by up to 84%) after exposure to the cannabinoid agonist (+)-WIN55212, in a concentration-dependent (0.1-1 µM) and stereoselective manner. Inhibition was maximal at 16 hr and abolished in the presence of SR141716A, a selective CB₁ receptor antagonist. Methanandamide (an analog of an endogenous cannabinoid, anandamide) also reduced cell surface labeling (by 43% at 1 µM). Differential labeling of cell surface and intracellular pools of receptor demonstrated that the reduction in cell surface immunoreactivity reflects agonist-induced internalization and suggests that the internalized CB₁ receptors are translocated toward the soma. The internalization process did not require activated G-protein (i) or (o) subunits. A different pattern of cell surface CB₁ receptor expression was observed using an undifferentiated F-11 cell line, which had pronounced somatic labeling. In these cells substantial CB₁ receptor internalization was also observed after exposure to (+)-WIN55212 (1 µM) for relatively short periods (30 min) of agonist exposure. In summary, this dynamic modulation of CB₁ receptor expression may play an important role in the development of cannabinoid tolerance in the CNS. Agonist-induced internalization at presynaptic terminals has important implications for the modulatory effects of G-protein-coupled receptors on neurotransmitter release.

Key words: internalization; cannabinoid; receptor trafficking; CB1; hippocampal; F-11

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/2172425-09$05.00/0

This article has been cited by other articles:

				I. Gomes, J. S. Grushko, U. Golebiewska, S. Hoogendoorn, A. Gupta, A. S. Heimann, E. S. Ferro, S. Scarlata, L. D. Fricker, and L. A. Devi Novel endogenous peptide agonists of cannabinoid receptors FASEB J, September 1, 2009; 23(9): 3020 - 3029. [Abstract] [Full Text] [PDF]

				M. M.C. van der Lee, M. Blomenrohr, A. A. van der Doelen, J. W.Y. Wat, N. Smits, B. J. Hanson, C. J. van Koppen, and G. J.R. Zaman Pharmacological Characterization of Receptor Redistribution and {beta}-Arrestin Recruitment Assays for the Cannabinoid Receptor 1 J Biomol Screen, August 1, 2009; 14(7): 811 - 823. [Abstract] [PDF]

				H.-C. Lin, S.-C. Mao, P.-S. Chen, and P.-W. Gean Chronic cannabinoid administration in vivo compromises extinction of fear memory Learn. Mem., December 2, 2008; 15(12): 876 - 884. [Abstract] [Full Text] [PDF]

				L. Mikasova, L. Groc, D. Choquet, and O. J. Manzoni Altered surface trafficking of presynaptic cannabinoid type 1 receptor in and out synaptic terminals parallels receptor desensitization PNAS, November 25, 2008; 105(47): 18596 - 18601. [Abstract] [Full Text] [PDF]

				I. A. Khasabova, S. G. Khasabov, C. Harding-Rose, L. G. Coicou, B. A. Seybold, A. E. Lindberg, C. D. Steevens, D. A. Simone, and V. S. Seybold A Decrease in Anandamide Signaling Contributes to the Maintenance of Cutaneous Mechanical Hyperalgesia in a Model of Bone Cancer Pain J. Neurosci., October 29, 2008; 28(44): 11141 - 11152. [Abstract] [Full Text] [PDF]

				B. A. S. Reyes, R. J. Valentino, and E. J. Van Bockstaele Stress-Induced Intracellular Trafficking of Corticotropin-Releasing Factor Receptors in Rat Locus Coeruleus Neurons Endocrinology, January 1, 2008; 149(1): 122 - 130. [Abstract] [Full Text] [PDF]

				H. D. Burns, K. Van Laere, S. Sanabria-Bohorquez, T. G. Hamill, G. Bormans, W.-s. Eng, R. Gibson, C. Ryan, B. Connolly, S. Patel, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor PNAS, June 5, 2007; 104(23): 9800 - 9805. [Abstract] [Full Text] [PDF]

				T. Bushell The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders J. Physiol., May 15, 2007; 581(1): 7 - 16. [Abstract] [Full Text] [PDF]

				A. Tappe-Theodor, N. Agarwal, I. Katona, T. Rubino, L. Martini, J. Swiercz, K. Mackie, H. Monyer, D. Parolaro, J. Whistler, et al. A Molecular Basis of Analgesic Tolerance to Cannabinoids J. Neurosci., April 11, 2007; 27(15): 4165 - 4177. [Abstract] [Full Text] [PDF]

				N. A. McDonald, C. M. Henstridge, C. N. Connolly, and A. J. Irving An Essential Role for Constitutive Endocytosis, but Not Activity, in the Axonal Targeting of the CB1 Cannabinoid Receptor Mol. Pharmacol., April 1, 2007; 71(4): 976 - 984. [Abstract] [Full Text] [PDF]

				L. Martini, M. Waldhoer, M. Pusch, V. Kharazia, J. Fong, J. H. Lee, C. Freissmuth, and J. L. Whistler Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G-protein-coupled receptor-associated sorting protein GASP1 FASEB J, March 1, 2007; 21(3): 802 - 811. [Abstract] [Full Text] [PDF]

				L. J. Sim-Selley, N. S. Schechter, W. K. Rorrer, G. D. Dalton, J. Hernandez, B. R. Martin, and D. E. Selley Prolonged Recovery Rate of CB1 Receptor Adaptation after Cessation of Long-Term Cannabinoid Administration Mol. Pharmacol., September 1, 2006; 70(3): 986 - 996. [Abstract] [Full Text] [PDF]

				C. Leterrier, J. Laine, M. Darmon, H. Boudin, J. Rossier, and Z. Lenkei Constitutive activation drives compartment-selective endocytosis and axonal targeting of type 1 cannabinoid receptors. J. Neurosci., March 22, 2006; 26(12): 3141 - 3153. [Abstract] [Full Text] [PDF]

				M. Bari, N. Battista, F. Fezza, A. Finazzi-Agro, and M. Maccarrone Lipid Rafts Control Signaling of Type-1 Cannabinoid Receptors in Neuronal Cells: IMPLICATIONS FOR ANANDAMIDE-INDUCED APOPTOSIS J. Biol. Chem., April 1, 2005; 280(13): 12212 - 12220. [Abstract] [Full Text] [PDF]

				G. L. McLemore, R. Z. B. Cooper, K. A. Richardson, A. V. Mason, C. Marshall, F. J. Northington, and E. B. Gauda Cannabinoid receptor expression in peripheral arterial chemoreceptors during postnatal development J Appl Physiol, October 1, 2004; 97(4): 1486 - 1495. [Abstract] [Full Text] [PDF]

				C. Leterrier, D. Bonnard, D. Carrel, J. Rossier, and Z. Lenkei Constitutive Endocytic Cycle of the CB1 Cannabinoid Receptor J. Biol. Chem., August 20, 2004; 279(34): 36013 - 36021. [Abstract] [Full Text] [PDF]

				J. P. McLaughlin, M. Xu, K. Mackie, and C. Chavkin Phosphorylation of a Carboxyl-terminal Serine within the {kappa}-Opioid Receptor Produces Desensitization and Internalization J. Biol. Chem., September 5, 2003; 278(36): 34631 - 34640. [Abstract] [Full Text] [PDF]

				H. Andersson, A. M. D'Antona, D. A. Kendall, G. Von Heijne, and C.-N. Chin Membrane Assembly of the Cannabinoid Receptor 1: Impact of a Long N-Terminal Tail Mol. Pharmacol., September 1, 2003; 64(3): 570 - 577. [Abstract] [Full Text] [PDF]

				M. Kouznetsova, B. Kelley, M. Shen, and S. A. Thayer Desensitization of Cannabinoid-Mediated Presynaptic Inhibition of Neurotransmission Between Rat Hippocampal Neurons in Culture Mol. Pharmacol., March 1, 2002; 61(3): 477 - 485. [Abstract] [Full Text] [PDF]

				C.-C. Huang, Y.-L. Chen, S.-W. Lo, and K.-S. Hsu Activation of cAMP-Dependent Protein Kinase Suppresses the Presynaptic Cannabinoid Inhibition of Glutamatergic Transmission at Corticostriatal Synapses Mol. Pharmacol., March 1, 2002; 61(3): 578 - 585. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help