gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Urotensin II-receptors schow rapid desensitization after stimulation with Urotensin II

Der Urotenin Rezeptor zeigt eine schnelle Desensitisierung nach Stimulation mit Urotensin II

Meeting Abstract (Hypertonie 2004)

  • G. Giebing - Med. Klinik IV - Charite, Campus Benjamin Franklin (Berlin, D)
  • M. Tölle - Med. Klinik IV - Charite, Campus Benjamin Franklin (Berlin, D)
  • W. Zidek - Med. Klinik IV - Charite, Campus Benjamin Franklin (Berlin, D)
  • M. van der Giet - Med. Klinik IV - Charite, Campus Benjamin Franklin (Berlin, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP118

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch118.shtml

Veröffentlicht: 10. August 2005

© 2005 Giebing et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Urotensin II (U-II) is the most potent vasoconstrictive peptide known so far. It has been repeatedly demonstrated that Urotensin II plays an important role in vascular tone regulation. Until now only little information is available about signaltranscuction and function of the UT-receptor (UT) which is activated by U-II. We investigated the receptor internalisation after stimulation with U-II.

Desensitization of UT was shown in arotic tension experiments using a small vessel myograph. A fusion protein consisting of the UT-receptor and the enhanced green fluorescent protein (EGFP) was used to invstigate the ligand-mediated internalization of the UT-receptor.

U-II induced a dose dependent vasoconstriction in rat thoracic aortae (EC ([-log mol] 9.0±0.2). Submaximal vasoconstriction of U-II was observed at concentrations of 10nmol/L. Application of 10nmol/L induced a rapid and stable contraction for at least 60min. 15min of repetitive washing reduced tension to baseline. Reapplication of UT after 30min showed a vasoconstriction which was 40% of initial vasoconstriction. Reapplication of UT after 120 min showed a vasoconstriction which was about 100% of initial vasoconstriction. Using HEK293 cells transiently expression UT/EGFP it could be demonstrated that UT-receptor shows a rapid internalization via a recycling pathway as demonstrated by the colocalization of UT/EGFP with the fluorescent transferring. Binding studies with UT/EGFP revealed a rapid internalization of receptor. About 50% of UT-receptors are internalized after stimulation with 10nmol/l UT for 30min. 100% of UT/EGFP binding sites were again demonstrable at the cell surface after 60 min.

We can demonstrate that UT-receptors show a rapid but not complete desensitization due to stimulation with U-II. UT-receptors are internalized via a recycling pathway. There is a rapid resensitization of UT-receptors. This mechanism is important for cardiovascular disease to unterstand the action of U-II on UT-receptors.