Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists.

ABSTRACT: Agonists of the nociceptin/orphanin FQ opioid peptide (NOP) receptor, a member of the opioid receptor family, are under active investigation as novel analgesics, but their modes of signaling are less well characterized than those of other members of the opioid receptor family. Therefore, we investigated whether different NOP receptor ligands showed differential signaling or functional selectivity at the NOP receptor. Using newly developed phosphosite-specific antibodies to the NOP receptor, we found that agonist-induced NOP receptor phosphorylation occurred primarily at four carboxyl-terminal serine (Ser) and threonine (Thr) residues, namely, Ser³⁴⁶, Ser³⁵¹, Thr³⁶², and Ser³⁶³, and proceeded with a temporal hierarchy, with Ser³⁴⁶ as th

SUBMITTER: Mann A 

PROVIDER: S-EPMC6934085 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature