A Molecular Basis of Analgesic Tolerance to Cannabinoids
作者： A. Tappe-Theodor , N. Agarwal , I. Katona , T. Rubino , L. Martini
DOI: 10.1523/JNEUROSCI.5648-06.2007
关键词:
摘要: Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets after repeated dosage. Analgesic to vivo could be caused agonist-induced downregulation intracellular trafficking cannabinoid receptors, but little known about molecular mechanisms involved. We show here type 1 receptor (CB1) interacts physically with G-protein-associated sorting protein (GASP1), a sorts receptors lysosomal compartments destined for degradation. CB1-GASP1 interaction was observed required CB1 spinal neurons ex as well vivo. Importantly, uncoupling from GASP1 mice abrogated toward cannabinoid-induced analgesia. These results suggest key regulator fate agonist exposure nervous system critically determines analgesic cannabinoids.
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