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  • Title: The role of GM1 ganglioside in regulating excitatory opioid effects.
    Author: Wu G, Lu ZH, Wei TJ, Howells RD, Christoffers K, Ledeen RW.
    Journal: Ann N Y Acad Sci; 1998 Jun 19; 845():126-38. PubMed ID: 9668347.
    Abstract:
    Our studies with cultured cells have provided new insight into the particular role of GM1 in regulating excitatory opioid responses. GM1 is significantly elevated in chronic opioid-treated cells via Gs/adenylyl cyclase activation. Such GM1 elevation promotes coupling of opioid receptor with Gs, resulting in attenuation of inhibitory opioid effects and induction of a sustained excitatory response. Application of exogenous GM1, but not other gangliosides, induces excitatory opioid responses not only in neurons and neuroblastoma cells that bear intrinsic opioid receptors but also in nonneuronal cells that are transfected with delta-opioid receptor. The latter system provides evidence that allosteric binding of GM1 changes receptor conformation from a Gi-coupled to a Gs-coupled mode. This is supported by preliminary experiments with a mutated delta-opioid receptor.
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