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