Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes.

Pearson, David; Shively, John E.; Clark, Brian R.; Geschwind, Irving I.; Barkley, M. S.; Nishioka, Richard S.; Bern, Howard A.

doi:10.1073/pnas.77.8.5021

Cited by 346 publications

(233 citation statements)

References 25 publications

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“…U-II was originally puri®ed from goby (Gillichthys mirabilis) urophysis extracts (Bern & Lederis, 1969;Pearson et al, 1980). Although this highly innervated and vascularized neurosecretory gland is believed to represent a vestigial organ, it is analogous in structure and function to the mammalian hypothalamo-neurohypophysial axis (Lederis, 1984;Bern et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

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

Douglas

Sulpizio

Piercy

et al. 2000

British J Pharmacology

212

176

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1 Urotensin-II (U-II) and its G-protein-coupled receptor, GPR14, are expressed within mammalian cardiac and peripheral vascular tissue and, as such, may regulate mammalian cardiovascular function. The present study details the vasoconstrictor pro®le of this cyclic undecapeptide in di erent vascular tissues isolated from a diverse range of mammalian species (rats, mice, dogs, pigs, marmosets and cynomolgus monkeys). 2 The vasoconstrictor activity of human U-II was dependent upon the anatomical origin of the vessel studied and the species from which it was isolated. In the rat, constrictor responses were most pronounced in thoracic aortae and carotid arteries: 7log[EC 50 ]s 9.09+0.19 and 8.84+0.21, R max s 143+21 and 67+26% 60 mM KCl, respectively (compared, for example, to 7log[EC 50 ] 7.90+0.11 and R max 142+12% 60 mM KCl for endothelin-1 [ET-1] in thoracic aortae). Responses were, however, absent in mice aortae (7log [EC 50 ] 56.50). These ®ndings were further contrasted by the observation that U-II was a`coronary-selective' spasmogen in the dog (7log [EC 50 ] 9.46+0.11, R max 109+23% 60 mM KCl in LCX coronary artery), yet exhibited a broad spectrum of vasoconstrictor activity in arterial tissue from Old World monkeys (7log [EC 50 ]s range from 8.96+0.15 to 9.92+0.13, R max s from 43+16 to 527+135% 60 mM KCl). Interestingly, signi®cant di erences in reproducibility and vasoconstrictor e cacy were seen in tissue from pigs and New World primates (vessels which responded to noradrenaline, phenylephrine, KCl or ET-1 consistently). 3 Thus, human U-II is a potent, e cacious vasoconstrictor of a variety of mammalian vascular tissues. Although signi®cant species/anatomical variations exist, the data support the hypothesis that U-II in¯uences the physiological regulation of mammalian cardiovascular function. British Journal of Pharmacology (2000) 131, 1262 ± 1274 Keywords: Urotensin-II; GPR14; SENR; endothelin-1; somatostatin; vascular reactivity; spasmogen; coronary artery; endothelium; vasoconstriction Abbreviations: FLIPR,¯uorescent imaging plate reader; GPCR, guanosine triphosphate-binding protein [G-protein]-coupled receptor; LAD coronary artery, left anterior descending coronary artery; LCX, left circum¯ex coronary artery; SENR, sensory epithelial neuropeptide-like receptor; U-II, Urotensin-II IntroductionThe integrated control of cardiovascular homeostasis is achieved through a combination of direct neuronal control and systemic activation of the neurohumoral axis. The principal mammalian vasoactive factors of this axis (angiotensin-II, endothelin [ET]-1, noradrenaline) exert their haemodynamic e ects exclusively via interactions with speci®c seven transmembrane heterotrimeric G-protein-coupled receptors (GPCRs). Drugs which antagonize such interactions constitute one of the most successful classes of therapeutic agents identi®ed to date (Stadel et al., 1997; Wilson et al., 1998). Nowhere is this more evident than within the vasculature where numerous agents have been developed successfully for the clinical ...

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Section: Discussionmentioning

confidence: 99%

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

Douglas

Sulpizio

Piercy

et al. 2000

British J Pharmacology

212

176

View full text Add to dashboard Cite

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“…Urotensin-II (U-II), a cyclic peptide first isolated from the teleost fish urophysis (Pearson et al 1980), has been described as an important vascular tone modulator in various species . U-II exerts its biological actions by interacting with specific plasma membrane receptors, identified as the orphan receptor GRP14 (Ames et al 1999).…”

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confidence: 99%

Urotensin‐II regulates intracellular calcium in dissociated rat spinal cord neurons

Filipeanu

Brǎiloiu

Dun

et al. 2002

Journal of Neurochemistry

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Urotensin-II (U-II), a peptide with multiple vascular effects, is detected in cholinergic neurons of the rat brainstem and spinal cord. Here, the effects of U-II on [Ca 2+ ] i was examined in dissociated rat spinal cord neurons by fura 2 microfluorimetry. The neurons investigated were choline acetyltransferasepositive and had morphological features of motoneurons. U-II induced [Ca 2+ ] i increases in these neurons with a threshold of 10 )9 M, and a maximal effect at 10 )6 M with an estimated EC 50 of 6.2 · 10 )9 M. The [Ca 2+ ] i increase induced by U-II was mainly caused by Ca 2+ influx from extracellular space, as the response was markedly attenuated in a Ca 2+ -free medium. Omega-conotoxin GVIA (10 )7 M), a N-type Ca 2+ channel blocker, largely inhibited these increases, whereas the P/Q Ca 2+ channel blocker, omega-conotoxin GVIIC (10 )7 M) and the L-type Ca 2+ channel blocker, verapamil (10 )5 M) had minimal effects. Down-regulation of protein kinase C by 4-aphorbol 12-myristate 13-acetate (10 )6 M) or enzyme inhibition using the specific inhibitor bisindolylmaleimide I (10 )6 M) did not inhibit the observed effects. Similarly, inhibition of protein kinase G with KT5823 (10 )6 M) or Rp-8-pCPT-cGMPS (3 · 10 )5 M) did not modify U-II-induced [Ca 2+ ] i increases. In contrast, protein kinase A inhibitors KT5720 (10 )6 M) and Rp-cAMPS (3 · 10 )5 M) reduced the response to 25 ± 3% and 42 ± 8%, respectively. Present results demonstrate that U-II modulates [Ca 2+ ] i in rat spinal cord neurons via protein kinase A cascade.

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“…The small vasoactive peptide urotensin II (UII) was originally characterised in fish [1]. The UII receptor (UT) was identified as the previously orphaned receptor G-protein coupled receptor 14 (GPR14) [2][3][4][5] or sensory epithelium neuropeptide-like receptor (SENR) [6] and is now named UT [7].…”

Section: Introductionmentioning

confidence: 99%

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

et al. 2013

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Aims/hypothesis The small, highly conserved vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis. However, its effects in diabetes-associated atherosclerosis have not been assessed. Methods Endothelial cells were grown in normal-and highglucose (5 and 25 mmol/l) media with and without UII (10 −8 mol/l) and/or the UII receptor antagonist, SB-657510 (10 −8 mol/l). Apoe knockout (KO) mice with or without streptozotocin-induced diabetes were treated with or without SB-657510 (30 mgkg −1 day −1 ; n=20 per group) and followed for 20 weeks. Carotid endarterectomy specimens from diabetic and non-diabetic humans were also evaluated. Results In high (but not normal) glucose medium, UII significantly increased CCL2 (encodes macrophage chemoattractant protein 1 [MCP-1]) gene expression (human aortic endothelial cells) and increased monocyte adhesion (HUVECs). UII receptor antagonism in diabetic Apoe KO mice significantly attenuated diabetes-associated atherosclerosis and aortic staining for MCP-1, F4/80 (macrophage marker), cyclooxygenase-2, nitrotyrosine and UII. UII staining was significantly increased in carotid endarterectomies from diabetic compared with non-diabetic individuals, as was staining for MCP-1. Conclusions/interpretation This is the first report to demonstrate that UII is increased in diabetes-associated atherosclerosis in humans and rodents. Diabetes-associated plaque development was attenuated by UII receptor antagonism in the experimental setting. Thus UII may represent a novel therapeutic target in the treatment of diabetes-associated atherosclerosis.

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Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes.

Cited by 346 publications

References 25 publications

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

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

Urotensin‐II regulates intracellular calcium in dissociated rat spinal cord neurons

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

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