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          Institute: MPI für medizinische Forschung     Collection: Abteilung Molekulare Neurobiologie     Display Documents



ID: 350189.0, MPI für medizinische Forschung / Abteilung Molekulare Neurobiologie
A molecular basis of analgesic tolerance to cannabinoids
Translation of Title:A molecular basis of analgesic tolerance to cannabinoids
Authors:Tappe−Theodor, Anke; Agarwal, Nitin; Katona, István; Rubino, Tiziana; Martini, Lene; Swiercz, Jakub; Mackie, Ken; Monyer, Hannah; Parolaro, Daniela; Whistler, Jennifer; Kuner, Thomas; Kuner, Rohini
Language:English
Date of Publication (YYYY-MM-DD):2007-04-11
Title of Journal:Journal of Neuroscience
Journal Abbrev.:J. Neurosci.
Volume:27
Start Page:4165
End Page:4177
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets in after repeated dosage. Analgesic tolerance to cannabinoids in vivo could be caused by agonist−induced downregulation and intracellular trafficking of cannabinoid receptors, but little is known about the molecular mechanisms involved. We show here that the type 1 cannabinoid receptor (CB1) interacts physically with G−protein−associated sorting protein 1 (GASP1), a protein that sorts receptors in lysosomal compartments destined for degradation. CB1−GASP1 interaction was observed to be required for agonist−induced downregulation of CB1 in spinal neurons ex vivo as well as in vivo. Importantly, uncoupling CB1 from GASP1 in mice in vivo abrogated tolerance toward cannabinoid−induced analgesia. These results suggest that GASP1 is a key regulator of the fate of CB1 after agonist exposure in the nervous system and critically determines analgesic tolerance to cannabinoids.
Free Keywords:cannabinoid receptor 1; receptor trafficking; protein−protein interactions; endocytosis; GASP; spinal nociception
Last Change of the Resource (YYYY-MM-DD):--
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie
Identifiers:LOCALID:7139
URI:http%3A%2F%2Fwww.jneurosci.org%2Fcgi%2Freprint%2F2...
URI:http%3A%2F%2Fwww.jneurosci.org%2Fcgi%2Fcontent%2Ff...
URI:http%3A%2F%2Fwww.jneurosci.org%2Fcgi%2Fcontent%2Fa...
DOI:10.1523%2FJNEUROSCI.5648-06.2007
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