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

2000; Wiley; Volume: 131; Issue: 3 Linguagem: Inglês

10.1038/sj.bjp.0703601

1476-5381

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

Hormonal Regulation and Hypertension

We have determined the distribution of receptors for human urotensin‐II (U‐II) in human and rat CNS and peripheral tissues. In rat, [ 125 I]‐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 [ 125 I]‐U‐II bound to a single receptor population with K D =0.24±0.17 n M and B max =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 EC 50 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 [ 125 I]‐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