Abstract
Internalization and downregulation are important steps in the modulation of receptor function. Recent work with the β2 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.
Original language | English (US) |
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Pages (from-to) | 19-27 |
Number of pages | 9 |
Journal | DNA and Cell Biology |
Volume | 19 |
Issue number | 1 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology