Details

Autor(en) / Beteiligte

• Maguire, Janet J
• Kuc, Rhoda E
• Davenport, Anthony P

Titel

Orphan‐receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin‐1

Ist Teil von

• British journal of pharmacology, 2000-10, Vol.131 (3), p.441-446

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2000

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• We have determined the distribution of receptors for human urotensin‐II (U‐II) in human and rat CNS and peripheral tissues. In rat, [125I]‐U‐II binding density was highest in the abducens nucleus of brainstem (139.6±14 amol mm−2). Moderate levels were detected in dorsal horn of spinal cord and lower levels in aorta (22.5±6 amol mm−2). In human tissues density was highest in skeletal muscle and cerebral cortex (∼30 amol mm−2), with lower levels (<15 amol mm−2) in kidney cortex and left ventricle. Little binding was identified in atria, conducting system of the heart and lung parenchyma. Receptor density was less in human coronary artery smooth muscle (14.6±3 amol mm−2, n=10) than rat aorta with no significant difference between normal and atherosclerotic vessels. In human skeletal muscle [125I]‐U‐II bound to a single receptor population with KD=0.24±0.17 nM and Bmax=1.97±1.1 fmol mg−1 protein (n=4). U‐II contracted human coronary, mammary and radial arteries, saphenous and umbilical veins with sub‐nanomolar EC50 values. U‐II was 50 times more potent in arteries and <10 times more potent in veins than endothelin‐1 (ET‐1). The maximum response to U‐II (∼20% of control KCl) was significantly less than to ET‐1 (∼80% KCl). In contrast, in rat aorta, U‐II and ET‐1 were equipotent with similar maximum responses. This is the first report of high affinity receptors for [125I]‐U‐II in human CNS and peripheral tissues. This peptide produces potent, low efficacy, vasoconstriction in human arteries and veins. These data suggest a potential role for U‐II in human physiology. British Journal of Pharmacology (2000) 131, 441–446; doi:10.1038/sj.bjp.0703601