Details

Autor(en) / Beteiligte

• Giebing, Günter
• Tölle, Markus
• Jürgensen, Jana
• Eichhorst, Jenny
• Furkert, Jens
• Beyermann, Michael
• Neuschäfer-Rube, Frank
• Rosenthal, Walter
• Zidek, Walter
• van der Giet, Markus
• Oksche, Alexander

Titel

Arrestin-Independent Internalization and Recycling of the Urotensin Receptor Contribute to Long-Lasting Urotensin II–Mediated Vasoconstriction

Ist Teil von

• Circulation research, 2005-09, Vol.97 (7), p.707-715

Ort / Verlag

Hagerstown, MD: American Heart Association, Inc

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• Urotensin II (UII), which acts on the G protein-coupled urotensin (UT) receptor, elicits long-lasting vasoconstriction. The role of UT receptor internalization and intracellular trafficking in vasoconstriction has yet not been analyzed. Therefore, UII-mediated contractile responses of aortic ring preparations in wire myography and rat UT (rUT) receptor internalization and intracellular trafficking in binding and imaging analyses were compared. UII elicited a concentration-dependent vasoconstriction of rat aorta (−log EC50, mol/L:9.0±0.1). A second application of UII after 30 minutes elicited a reduced contraction (36±4% of the initial response), but when applied after 60 minutes elicited a full contraction. In internalization experiments with radioactive labeled VII (I-UII), ≈70% of rUT receptors expressed on the cell surface of human embryonic kidney 293 cells were sequestered within 30 minutes (half life [th]5.6±0.2 minutes), but recycled quantitatively within 60 minutes (th 31.9±2.6 minutes). UII-bound rUT receptors were sorted to early and recycling endosomes, as evidenced by colocalization of rUT receptors with the early endosomal antigen and the transferrin receptor. Real-time imaging with a newly developed fluorescent UII (Cy3-UII) revealed that rUT receptors recruited arrestin3 green fluorescent protein to the plasma membrane. Arrestin3 was not required for the endocytosis of the rUT receptor, however, as internalization of Cy3-UII was not altered in mouse embryonic fibroblasts lacking endogenous arrestin2/arrestin3 expression. The data demonstrate that the rUT receptor internalizes arrestin independently and recycles quantitatively. The continuous externalization of rUT receptors provides the basis for repetitive and lasting UII-mediated vasoconstriction.