κ-Opioid Receptor Antibodies
Dynorphins are the endogenous ligands of the κ-opioid receptor (kappa-opioid receptor, KOP). U50,488H is a selective, high-efficacy κ-agonist. It has been proposed that G protein-biased kappa agonists such as nalfurafine or salvinorin B can reduce pain and itch, but exhibit fewer side effects such as sedation or dysphoria. KOP desensitization, trafficking and signaling are regulated by phosphorylation of carboxyl-terminal serine356/threonine357 (pS356/pT357-KOP) and threonine363 (pT363-KOP). Agonist-induced KOP phosphorylation can be mediated by multiple kinases including GRK2, GRK3, GRK5 and GRK6. S356 and T357 are also substrates for PKC-mediated phosphorylation. The designation of phosphorylation sites refers to the human KOP. This phosphorylation motif is also present in mice and rats. For more information on κ-opioid receptor pharmacology please refer to the IUPHAR database. For further reading refer to:
Chen C, Chiu YT, Wu W, Huang P, Mann A, Schulz S, Liu-Chen LY. Determination of sites of U50,488H-promoted phosphorylation of the mouse κ opioid receptor (KOPR): disconnect between KOPR phosphorylation and internalization. Biochem J. 2016 Feb 15;473(4):497-508. doi: 10.1042/BJ20141471. Epub 2015 Dec 3. PubMed PMID: 26635353; PubMed Central PMCID: PMC5444940.
Chiu YT, Chen C, Yu D, Schulz S, Liu-Chen LY. Agonist-Dependent and -Independent κ Opioid Receptor Phosphorylation: Distinct Phosphorylation Patterns and Different Cellular Outcomes. Mol Pharmacol. 2017 Nov;92(5):588-600. doi: 10.1124/mol.117.108555. Epub 2017 Sep 11. Erratum in: Mol Pharmacol. 2018 Aug;94(2):895. PubMed PMID: 28893975; PubMed Central PMCID: PMC5635518.