Contraction of major artery segments of rat by fish neuropeptide urotensin II
Itoh, H.; Itoh, Y.; Rivier, J.; Lederis, K.
American Journal of Physiology 252(2 Pt 2): R361-R366
1987
ISSN/ISBN: 0002-9513 PMID: 3812773 Document Number: 303071
Urotensin II (U II) caused marked concentration-dependent contraction of helical strips from several major arteries of the rat. The thoracic aorta was most sensitive; the apparent concentration of U II producing half-maximal contraction was 6.8 .times. 10-10 M. Papaverine, dibutyryl cyclic AMP, forskolin, and nitroprusside antagonized the contractile responses to U II at the apparent concentrations producing 50% inhibition (IC50) of 7.6 .times. 10-6, 2.1 .times. 10-4, 2.5 .times. 10-6 and 1.5 .times. 10-8 M, respectively. Verapamil, a calcium channel-blocking agent, partially inhibited the contractile response to U II at IC50 = 6.5 .times. 10-6 M. Maximal relaxation, i.e., a complete inhibition, could not be obtained even at a concentration of 3 .times. 10-5 M verapamil. Cyproheptadine reduced the U II-induced contraction at higher concentrations. Phentolamine (10-5 M), propranolol (10-5 M), atropine (10-4 M), tetrodotoxin (10-6 M), burimamide (10-5 M), and indomethacin (10-5 M) did not change the U II-induced contraction. At higher concentration, U II (10-8 M) induced a small contraction of aortic strips in Ca2+-free Krebs Henseleit solution similar to that of norepinephrine, but the U II-induced contraction was not inhibited by phentolamine of propranolol. The action of U II did not require the presence of endothelial cells. It is concluded that U II acts on vascular smooth muscle and induces the contraction partly through intracellular Ca2+ mobilization but mainly by stimulating the influx of extracellular Ca2+ via potential dependent and potential independent calcium channels. Partial sequences of the U II peptide U II5-12 and U II6-12 also contracted rat thoracic aorta with 50% effective dose values of 5.2 .times. 10-10 and 3.0 .times. 10-9 M, respectively. The fragment U II5-11 had only minimal contractile action at 10-7 M. It may be concluded that the partial sequence U II5-12 represents the minimum active core of the peptide to induce a full contractile response in the rat thoracic aorta.