Rats exposed to a single stressful event experience days-long constitutive activation of the kappa opioid receptor at inhibitory synapses in part of the brain’s reward system, which increases their drug-seeking behavior.
Pro-nociceptive and pro-inflammatory TRPM3 (transient receptor potential melastatin 3) channels, expressed in somatosensory neurons, are inhibited by activation of Gαi-coupled receptors, such as µ-opioid receptors, in vitro and in vivo.
Opioid sensitive neurons were identified using a traceless affinity labeling strategy to covalently label endogenous mu-opioid receptors with fluorescent compounds in living brain slices from wild type animals.
The structure-based design established a new approach to control pathway-selective activation of opioid receptors, resulting in new dual MOR/KOR G-protein biased agonist analgesics with attenuated liabilities.
By differentially modulating the two major excitatory inputs to the striatum, mu- and delta-opioid receptors regulate the balance between thalamic and cortical inputs to the striatum.
A GPCR activated by the same agonist engages different conformational biosensors at different subcellular locations, suggesting that location-based conformations drive spatial encoding of signaling.
Different dynorphins, which signal similarly from the cell surface, can differentially localize G protein-coupled receptors to specific subcellular compartments and cause divergent receptor fates and distinct spatiotemporal patterns of signaling.
