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.
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 trace amine-associated receptor 1 gene has a causal role in methamphetamine intake and thermal response, and interacts with the mu-opioid receptor gene in its methamphetamine addiction-related effects.
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.
Activation of mu-opioid receptors in the nucleus accumbens by their endogenous ligands promotes consumption of high-fat food in sated but not hungry rats, via enhancement of a neural signal that promotes cued approach behavior.
Administration of dopamine and opioid receptor antagonists resulted in reduced reward anticipation (effort and increased negative facial reactions), but only administration of opioid antagonists resulted in reduced liking (facial reactions).
Linking deep mutational scanning with engineered transcriptional reporters in human cell lines establishes a generalizable method for exploring pharmacogenomics, structure, and function across broad classes of drug receptors.