title: Kappa opioid receptor endocytosis by dynorphin peptides.
abstract: Internalization and downregulation are important steps in the modulation of receptor function. Recent work with the beta2 adrenergic and opioid receptors have implicated these processes in receptor-mediated activation of mitogen-activated protein kinase (MAPK). We have used CHO cells expressing epitope-tagged rat kappa opioid receptors (rKORs) and prodynorphin-derived peptides to characterize the agonist-mediated endocytosis of rKORs and activation of MAPK. Kappa receptor-selective peptides induced receptor internalization and downregulation whereas nonpeptide agonists did not. An examination of the ability of dynorphin A-17-related peptides (lacking C-terminal amino acids) to promote KOR internalization, inhibition of adenylyl cyclase, and MAPK phosphorylation revealed that the N-terminal seven residues play an important role in eliciting these responses. Both dynorphin peptides and nonpeptide agonists induced rapid and robust phosphorylation of MAPKs. Taken together, these results point to a difference in the ability of dynorphin peptides and nonpeptide ligands to promote rKOR endocytosis and support the view that rKOR internalization is not required for MAPK activation.
authors.affiliation: Department of Pharmacology, New York University School of Medicine, New York 10016, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Jordan
authors.forename: S
authors.initials: S
authors.lastname: Cvejic
authors.forename: L A
authors.initials: LA
authors.lastname: Devi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004399:Dynorphins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D004789:Enzyme Activation; D008024:Ligands; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*
chemical_list: D008024:Ligands; D010455:Peptides; D017473:Receptors, Opioid, kappa; D004399:Dynorphins; D020928:Mitogen-Activated Protein Kinases