Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors

Camarda, Valeria; Song, Wei; Marzola, Erika; Spagnol, Martina; Guerrini, Remo; Salvadori, Severo; Regoli, Doménico; Thompson, Jonathan P.; Rowbotham, David J.; Behm, David J.; Douglas, Stephen A.; Calò, Girolamo; Lambert, David G.

doi:10.1016/j.ejphar.2004.07.089

Cited by 56 publications

(71 citation statements)

References 12 publications

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“…10, compound 9), which does not evoke any contraction of thoracic aorta rings, shifts to the right the UII concentration-response curve (Camarda et al, 2006). However, UFP-803 is about 10-fold less potent than urantide to antagonize UII-induced contraction (Patacchini et al, 2003;Camarda et al, 2004Camarda et al, , 2006. The cyclic somatostatin analog SB-710411, i.e., Cpa-c[DLys-PalDTrp-Lys-Val-Cys]Cpa-NH 2 (Cpa: 4-chlorophenylalanine; Pal: 3-pyridylalanine; Coy et al, 2000;Fig.…”

Section: Structure-activity Relationshipsmentioning

confidence: 99%

“…Finally, replacement of the Tyr 9 residue in the P5U sequence with the benzothiazolyl-alanine or the (3,4-Cl)Phe moities leads to analogs with pEC 50 values at least 1.4 log higher than that of P5U being the most potent UT agonists discovered to date (Carotenuto et al, 2014 Fig. 10, compound 8) acts as a UT antagonist in the rat aorta bioassay (Patacchini et al, 2003;Camarda et al, 2004) but stimulates Ca 2+ mobilization in CHO cells transfected with human UT Grieco et al, 2005 ]UII (4)(5)(6)(7)(8)(9)(10)(11) ; Fig. 10, compound 9), which does not evoke any contraction of thoracic aorta rings, shifts to the right the UII concentration-response curve (Camarda et al, 2006).…”

Section: Structure-activity Relationshipsmentioning

confidence: 99%

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International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

et al. 2014

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Section: Structure-activity Relationshipsmentioning

confidence: 99%

Section: Structure-activity Relationshipsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

et al. 2014

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“…However, urantide is considered a low-efficacy partial agonist according to the fact that it mimicked the effects of U-II on [Ca 2ϩ ] i release in Chinese hamster ovary (CHO) cells stably expressing the hUT receptor (CHO hUT cells). 42 The different pharmacological behavior of urantide (pure antagonist in human macrophages as well as rat aortic VSMCs versus partial agonist in CHO hUT cells) could be attributed to the amount of expression of hUT receptor. The efficacy of urantide on [Ca 2ϩ ] i release might be overestimated in the cell system expressing very high levels of recombinant receptors, whereas in human macrophages, where the density of UT sites is lower, it could not be detected.…”

Section: Limitationsmentioning

confidence: 99%

Human Urotensin II Accelerates Foam Cell Formation in Human Monocyte-Derived Macrophages

et al. 2005

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Abstract-Human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, and its receptor (UT) are involved in hypertension and atherosclerosis. Acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) converts intracellular free cholesterol into cholesterol ester (CE) for storage in lipid droplets and plays an important role in the formation of macrophage-derived foam cells in atherosclerotic lesions. We examined the effects of U-II on ACAT-1 expression and CE accumulation in human monocyte-derived macrophages. U-II increased ACAT activity in a concentration-dependent manner after 7 days in monocyte primary culture. Immunoblotting analysis showed that U-II at 25 nmol/L increased ACAT-1 protein expression level by 2.5-fold, which was completely abolished by anti-U-II antibody, selective UT receptor antagonists (urantide and 4-aminoquinoline), a G-protein inactivator (GDP-␤-S), a c-Src protein tyrosine kinase inhibitor (PP2), a protein kinase C (PKC) inhibitor (rottlerin), a mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059), or a Rho kinase (ROCK) inhibitor (Y27632). Northern blotting analysis indicated that among the 4 ACAT-1 mRNA transcripts (2.8-, 3.6-, 4.3-, and 7.0-kb), the 2.8-and 3.6-kb transcript levels were selectively upregulated by Ϸ1

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“…Accordingly, the aim of the current study was to determine the effect of exogenous UII on renal function in the SHR. We also determined the contributions of endogenous UII to renal function by blocking the UT receptor with urantide, a full antagonist of the rat UT receptor (5). Finally, we quantified mRNA expression of UII and UT and localized protein expression by immunohistochemistry in SHR and control Wistar-Kyoto (WKY) rat kidneys.…”

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confidence: 99%

Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II

Abdel-Razik¹,

Balment²,

Ashton³

2008

American Journal of Physiology-Renal Physiology

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Abdel-Razik AE, Balment RJ, Ashton N. Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II. Am J Physiol Renal Physiol 295: F1239 -F1247, 2008. First published August 13, 2008 doi:10.1152/ajprenal.90374.2008.-Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol ⅐ min Ϫ1 ⅐ 100 g body wt Ϫ1 ) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (⌬GFR WKY, n ϭ 7, Ϫ0.3 Ϯ 0.1 vs. SHR, n ϭ 7, Ϫ0.6 Ϯ 0.1 ml ⅐ min Ϫ1 ⅐ 100 g body wt Ϫ1 , P ϭ 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (⌬FENa; ϩ0.6 Ϯ 0.1%, P ϭ 0.02) in contrast to SHR in which no such change was observed (⌬FENa Ϫ0.6 Ϯ 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (ϩ0.3 Ϯ 0.1) compared with WKY rats (ϩ0.1 Ϯ 0.1 ml ⅐ min Ϫ1 ⅐ 100 g body wt Ϫ1 , P ϭ 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.UT receptor; kidney; glomerular filtration rate; sodium THE NOVEL PEPTIDE hormone urotensin II (UII), originally identified in a neurohemal organ unique to fish (3), is now known to be expressed in many mammalian species, including humans (9) and rats (8). UII binds to a single specific G protein-coupled receptor (2, 18), designated the UT receptor (11), which is expressed abundantly in the nervous (13) and cardiorenal systems (20,30). The potent vasoconstrictor actions of UII (2) appear to be mediated by Ca 2ϩ mobilization through activation of a number of signaling pathways, including Ca 2ϩ channels, tyrosine kinase, p38MAPK, and ERK1/2 (26). UII also has a vasodepressor action, particularly in the rat, which is endothelium and nitric oxide dependent (26).UII has been implicated widely in cardiovascular disease. Plasma (7) and cerebrospinal fluid (31) UII concentrations have been positively correlated with blood pressure in hypertensive patients and single nucleotide polymorphisms of the UII gene have been associated with the development of essential hypertension (35). Elevated plasma or urinary UII concentrations have also been reported in patients with portal hypertension (15), congestive heart failure (22, 27), and renal failure (21, 32). These observations led to the suggestion that UII plays a role in card...

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Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors

Cited by 56 publications

References 12 publications

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

Human Urotensin II Accelerates Foam Cell Formation in Human Monocyte-Derived Macrophages

Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II

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