Morphine alters the selective association between mu-opioid receptors and specific RGS proteins in mouse periaqueductal gray matter

@article{Garzn2005MorphineAT,
  title={Morphine alters the selective association between mu-opioid receptors and specific RGS proteins in mouse periaqueductal gray matter},
  author={Javier Garz{\'o}n and Mar{\'i}a F Rodr{\'i}guez-Mu{\~n}oz and Pilar S{\'a}nchez-Bl{\'a}zquez},
  journal={Neuropharmacology},
  year={2005},
  volume={48},
  pages={853-868}
}

The Mu-Opioid Receptor and the NMDA Receptor Associate in PAG Neurons: Implications in Pain Control

It is reported that mu-opioid receptors (MOR) and NMDAR NR1 subunits associate in the postsynaptic structures of PAG neurons, a finding that could be exploited in developing bifunctional drugs that would act exclusively on those N MDARs associated with MORs.

RGS9-2 Modulates Responses to Oxycodone in Pain-Free and Chronic Pain States

It is demonstrated that RGS9-2 positively regulates the rewarding effects of oxycodone in pain-free states, and in a model of neuropathic pain, which provides new information on the signal-transduction mechanisms that modulate the rewarding and analgesic actions of oxy codone.

Effector antagonism by the regulators of G protein signalling (RGS) proteins causes desensitization of mu-opioid receptors in the CNS

The role played by RGS proteins in the intensity and duration of the effects of mu-opioid receptor agonists, and how they influence the delayed tolerance that develops in response to specific doses of opioids are reviewed.

Morphine induces endocytosis of neuronal μ-opioid receptors through the sustained transfer of Gα subunits to RGSZ2 proteins

In the nervous system, morphine induces a strong desensitization before promoting the phosphorylation and recycling of MORs, and recycled MORs recover the control on these Gα subunits and opioid tolerance develops slowly.

Direct association of Mu-opioid and NMDA glutamate receptors supports their cross-regulation: molecular implications for opioid tolerance.

This work proposes a model that incorporates the most relevant signaling components implicated in opioid tolerance in which, certain signals originating from the activated MOR are perceived by the associated NMDAR, which in turn exerts a negative feedback effect on MOR signaling.

Mu-Opioid Receptors Transiently Activate the Akt-nNOS Pathway to Produce Sustained Potentiation of PKC-Mediated NMDAR-CaMKII Signaling

The Akt-nNOS pathway acts as a primer for morphine-triggered events which leads to the sustained potentiation of the NMDAR-CaMKII pathway and MOR inhibition, ultimately leading to morphine tolerance.

The histidine triad nucleotide-binding protein 1 supports mu-opioid receptor–glutamate NMDA receptor cross-regulation

It is found that the MOR-associated histidine triad nucleotide-binding protein 1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR and may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms independent of N MDAR.

Regulators of G-Protein Signaling (RGS) Proteins Promote Receptor Coupling to G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels

The studies indicate that RGS proteins have multiple mechanisms of modulating GPCR signaling that produce negative and positive regulation of signaling depending on the effector, and this coupling is critical for opioid- and baclofen-mediated spinal antinociception.
...

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