Contraction of major artery segments of rat by fish neuropeptide urotensin II

Abstract

Urotensin II (U II) caused marked concentration-dependent contractions 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 X 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 X 10(-6), 2.1 X 10(-4), 2.5 X 10(-6), and 1.5 X 10(-8) M, respectively. Verapamil, a calcium channel-blocking agent, partially inhibited the contractile response to U II at IC50 = 6.5 X 10(-6) M. Maximal relaxation, i.e., a complete inhibition, could not be obtained even at a concentration of 3 X 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 or 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential vasoconstrictor activity of human urotensin‐II in vascular tissue isolated from the rat, mouse, dog, pig, marmoset and cynomolgus monkey

“…In accord with previous studies performed using the goby isoform of U-II in ®sh, amphibian and mammalian (rat and rabbit aortae) isolated vascular tissue (Muramatsu et al, 1979;Gibson, 1987;Gibson et al, 1988;Itoh et al, 1987;1991;Conlon et al, 1996), potent, sustained and e cacious vasoconstriction was observed upon exposure of speci®c rat, dog, pig and primate isolated blood vessels to the human isoform of U-II (Table 5). Indeed, human U-II was between 8 and 109 fold more potent than ET-1.…”

“…This hypothesis is supported by the recent identi®cation of U-II isopeptides in the rat, mouse, pig and man (Ames et al, 1999;Coulouarn et al, 1998;Mori et al, 1999). The present study has evaluated the functional activity of human U-II in a range of native vascular tissue isolated from a variety of mammals.In accord with previous studies performed using the goby isoform of U-II in ®sh, amphibian and mammalian (rat and rabbit aortae) isolated vascular tissue (Muramatsu et al, 1979;Gibson, 1987;Gibson et al, 1988;Itoh et al, 1987;1991;Conlon et al, 1996), potent, sustained and e cacious vasoconstriction was observed upon exposure of speci®c rat, dog, pig and primate isolated blood vessels to the human isoform of U-II (Table 5). Indeed, human U-II was between 8 and 109 fold more potent than ET-1.…”

“…by protein kinase-A/-C, putative receptor kinases, RGS proteins, arrestins, di erences in post-translational modi®cation etc. ).The possibility that U-II lacks a signi®cant (spare) receptor reserve in speci®c species or tissues is consistent with the observations of Itoh et al (1987; where determination of radioligand binding B max s and contractile R max s for goby U-II in rat isolated arteries revealed that modest changes in receptor density correlated with profound changes in contractile e cacy. This may constitute a potential physiological mechanism whereby the ability of U-II to regulate systemic vascular resistance can be modi®ed.…”

“…Further to this, the cyclic octapeptide core sequence of the U-II isopeptide family (D/E[CFWKYC]V/I), one which is absolutely conserved across all species identi®ed, is reported to constitute the minimum sequence required for the retention of full biological activity (Itoh et al, 1987;. This implies that the amino-tail of the U-II isopeptide family, a region divergent across species, does not grossly a ect ligand binding/function.…”

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

“…In agreement with these data, it has previously been reported that UII inhibits carbachol-induced contraction of the anococcygeous muscle (44) and that dbcAMP and forskolin counteract the contractile response evoked by UII in rat aortic strips (45). UII has also been shown to lower cytoplasmic free Ca 2þ concentration in goby enterocytes (46).…”