Kappa Opioid Receptor Endocytosis by Dynorphin Peptides

Jordan, Bryen A.; Cvejic, Svetlana; Devi, Lakshmi A.
January 2000
DNA & Cell Biology;Jan2000, Vol. 19 Issue 1, p19
Academic Journal
Internalization and downregulation are important steps in the modulation of receptor function. Recent work with the beta[sub 2] 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.


Related Articles

  • Recycling and Resensitization of Delta Opioid Receptors. Trapaidze, N.; Gomes, I.; Bansinath, M.; Devi, L.A. // DNA & Cell Biology;Apr2000, Vol. 19 Issue 4, p195 

    Exposure to opioids results in the activation of opioid receptors; this is followed by receptor endocytosis. Previously, we showed that delta opioid receptors undergo rapid agonist-mediated internalization and that mutations in the C-tail result in a substantial loss of agonist-mediated...

  • Opioid Peptide Deltorphin II Simulates the Cardioprotective Effect of Ischemic Preconditioning: Role of δ-Opioid Receptors, Protein Kinase C, and K Channels. Maslov, L.; Barzakh, E.; Krylatov, A.; Chernysheva, G.; Krieg, T.; Solenkova, N.; Lishmanov, A.; Cybulnikov, S.; Zhang, Y. // Bulletin of Experimental Biology & Medicine;May2010, Vol. 149 Issue 5, p591 

    The cardioprotective properties of a δ-opioid receptor agonist deltorphin II were studied in rats with coronary occlusion and reperfusion. Opioid receptor ligands and inhibitors (glybenclamide, chelerythrine, and 5-hydroxydecanoate) were injected intravenously before ischemia and reperfusion....

  • [Dmt�]DALDA is Highly Selective and Potent at � Opioid Receptors, but is not Cross-Tolerant with Systemic Morphine. Riba, Pal; Yong Ben, Pal; Nguyen, Thi M.-D.; Furst, Susanna; Schiller, Peter W.; Lee, Nancy M. // Current Medicinal Chemistry;Jan2002, Vol. 9 Issue 1, p31 

    The clinical effectiveness of morphine is limited by several side effects, including the development of tolerance and dependence. Most of these side effects are believed to be mediated by central opioid receptors therefore, hydrophilic opioids, which don't cross the blood-brain barrier, may have...

  • Another opiate for the masses? Julius, David // Nature;4/3/1997, Vol. 386 Issue 6624, p442 

    Provides background and analysis for a paper which reports the isolation of two mu-selective peptide ligands from mammalian brain that are mediated through the mu opioid receptor. The name of the peptides being endomorphin-1 and -2; The comparison of the peptides to morphine; The possible use...

  • Nociception. Kuner, Rohini // Encyclopedic Reference of Molecular Pharmacology;2004, p658 

    The term "nociceptin" is defined as an opioid peptide, the endogenous ligand for the opioid receptor-like protein.

  • Ligand-mediated endocytosis and intracellular sequestration of guanylyl cyclase/natriuretic peptide receptors: role of GDAY motif. Kailash Pandey // Molecular & Cellular Biochemistry;Jan2010, Vol. 334 Issue 1/2, p81 

    Abstract  The guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), also referred to as GC-A, is a single polypeptide molecule having a critical function in blood pressure regulation and cardiovascular homeostasis. GC-A/NPRA, which resides in the plasma membrane, consists...

  • Remote preconditioning by infrarenal aortic occlusion is operative via δ1-opioid receptors and free radicals in vivo in the rat heart Weinbrenner, Christof; Schulze, Falk; Sárváry, László; Strasser, Ruth H. // Cardiovascular Research;Feb2004, Vol. 61 Issue 3, p591 

    Background: Ischemic preconditioning (PC) is a powerful mechanism in reducing infarct size of the heart. Protection can be performed either by an ischemic stimulus of the heart itself or by ischemia of an organ distant to the heart (remote PC). We have previously shown that remote PC by...

  • Peripheral effects of morphine and expression of μ-opioid receptors in the dorsal root ganglia during neuropathic pain: nitric oxide signaling. Hervera, Arnau; Negrete, Roger; Leánez, Sergi; Martín-Campos, Jesús M.; Pol, Olga // Molecular Pain;2011, Vol. 7 Issue 1, p25 

    Background: The local administration of μ-opioid receptor (MOR) agonists attenuates neuropathic pain but the precise mechanism implicated in this effect is not completely elucidated. We investigated if nitric oxide synthesized by neuronal (NOS1) or inducible (NOS2) nitric oxide synthases...

  • Matrix Stiffness Affects Endocytic Uptake of MK2-Inhibitor Peptides. Brugnano, Jamie L.; Panitch, Alyssa // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    In this study, the role of substrate stiffness on the endocytic uptake of a cell-penetrating peptide was investigated. The cell-penetrating peptide, an inhibitor of mitogen-activated protein kinase activated protein kinase II (MK2), enters a primary mesothelial cell line predominantly through...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics