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

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 (125I-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-...