Expression and Functional Role of Urotensin-II and Its Receptor in the Adrenal Cortex and Medulla: Novel Insights for the Pathophysiology of Primary Aldosteronism

Giuliani, Luisa; Lenzini, Livia; Antonello, Michele; Aldighieri, Enrico; Belloni, Anna S.; Fassina, Ambrogio; Gómez-Sánchez, Celso E.; Rossi, Gian Paolo

doi:10.1210/jc.2008-1131

Cited by 27 publications

(25 citation statements)

References 33 publications

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“…Both unglycosylated (w42 kDa) and glycosylated (w60 kDa) forms of UTR protein have been identified in human adrenocortical tissues and COS-7 cells overexpressing UTR (Boucard et al 2003, Giuliani et al 2009). Ventricular samples from rats express the unglycosylated form of UTR, whereas the glycosylated form was the only immunoreactive UTR protein identified in rat kidneys, coronary arteries, and cultured coronary artery smooth muscle cells (Gong et al 2004, Abdel-Razik et al 2008b, DominguezRodriguez et al 2012.…”

Section: Discussionmentioning

confidence: 99%

Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

Soni¹,

Adebiyi²

2013

Journal of Endocrinology

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Renal expression of the peptide hormone urotensin II (UII) and its receptor (UTR) are dependent on kidney maturation and anatomical regions. However, renal regional hemodynamic effects of UII in neonates are unclear. Here, we investigated regional hemodynamic responses to acute intrarenal arterial administration of UII in newborn pigs. Western immunoblotting and immunofluorescence confirmed UTR expression and membrane localization in newborn pig renal afferent arterioles and afferent arteriolar smooth muscle cells respectively. Intrarenal arterial bolus injections of human UII (hUII; 1-100 ng/kg) resulted in a dose-dependent decrease in total renal blood flow (RBF) and an increase in mean arterial pressure (MAP) and renal vascular resistance (RVR) in newborn pigs. Moreover, hUII dose dependently reduced cortical blood flow (CBF) but increased medullary blood flow (MBF) in the piglets. hUII-induced MAP elevation and hemodynamic changes were inhibited by urantide, a UTR antagonist, but not losartan, a type 1 angiotensin II receptor antagonist. U-73122, a phospholipase C (PLC) inhibitor, and 2-aminoethoxydiphenyl borate, an inositol 1,4,5 trisphosphate (IP 3 ) receptor antagonist, attenuated hUII-induced MAP and RVR elevations, RBF and CBF reductions, but not MBF increase. These findings indicate that intrarenal arterial administration of hUII elevates blood pressure and induces region-selective renal hemodynamic changes in newborn pigs. Our data also suggest that the PLC/IP 3 signaling pathway contributes to hUII-induced alterations in MAP, RBF, RVR, and CBF but not MBF in newborn pigs.

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Section: Discussionmentioning

confidence: 99%

Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

Soni¹,

Adebiyi²

2013

Journal of Endocrinology

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“…Relative to one another, UII expression is increased in pheochromocytoma, whereas UT receptor expression is increased in the adenoma tissue (41). This may account for the clinically observed relationship between pheochromocytoma and primary aldosteronism (41).…”

Section: Pathological Significance Of Uiimentioning

confidence: 93%

“…Recently, pheochromocytoma and aldosterone-producing adenoma samples were obtained and compared by using realtime PCR and immunohistochemistry (41). Relative to one another, UII expression is increased in pheochromocytoma, whereas UT receptor expression is increased in the adenoma tissue (41).…”

Section: Pathological Significance Of Uiimentioning

confidence: 99%

Role of urotensin II in health and disease

Ross

McKendy

Giaid

2010

American Journal of Physiology-Regulatory, Integrative and Comp

128

107

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Urotensin II (UII) is an 11 amino acid cyclic peptide originally isolated from the goby fish. The amino acid sequence of UII is exceptionally conserved across most vertebrate taxa, sharing structural similarity to somatostatin. UII binds to a class of G protein-coupled receptor known as GPR14 or the urotensin receptor (UT). UII and its receptor, UT, are widely expressed throughout the cardiovascular, pulmonary, central nervous, renal, and metabolic systems. UII is generally agreed to be the most potent endogenous vasoconstrictor discovered to date. Its physiological mechanisms are similar in some ways to other potent mediators, such as endothelin-1. For example, both compounds elicit a strong vascular smooth muscle-dependent vasoconstriction via Ca 2ϩ release. UII also exerts a wide range of actions in other systems, such as proliferation of vascular smooth muscle cells, fibroblasts, and cancer cells. It also 1) enhances foam cell formation, chemotaxis of inflammatory cells, and inotropic and hypertrophic effects on heart muscle; 2) inhibits insulin release, modulates glomerular filtration, and release of catecholamines; and 3) may help regulate food intake and the sleep cycle. Elevated plasma levels of UII and increased levels of UII and UT expression have been demonstrated in numerous diseased conditions, including hypertension, atherosclerosis, heart failure, pulmonary hypertension, diabetes, renal failure, and the metabolic syndrome. Indeed, some of these reports suggest that UII is a marker of disease activity. As such, the UT receptor is emerging as a promising target for therapeutic intervention. Here, a concise review is given on the vast physiologic and pathologic roles of UII.UT receptor; somatostatin; human; experimental animals; autocrine/paracrine UROTENSIN II (UII) was initially isolated from the urophysis of the goby fish (Gillichthys mirabilis) (97). The peptide was subsequently isolated from the white sucker (Catostomus commersoni) and the carp (Cyprinus carpio). Although there were variations in the amino acid sequence near the amino terminus, in both species the UII molecule retained the COOH-terminal cyclic sequence: -Cys

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“…Takahashi et al (16) showed that UII and UT-R are expressed in glioblastoma cell line T98G, neuroblastoma cell line IMR32, choriocarcinoma cell line BeWo, adrenocortical carcinoma cell line SW-13, colorectal carcinoma cell line DLD-1, and cervical carcinoma cell line HeLa. UII and UT-R mRNA are also expressed in adrenal tumor (17,18), renal carcinoma (19), and pheochromocytoma (20,21). Furthermore, SW-13 cells has been demonstrated to secrete UII (16).…”

Section: Introductionmentioning

confidence: 99%

Expression of urotensin II and its receptor in human lung adenocarcinoma A549 cells and the effect of urotensin II on lung adenocarcinoma growth in vitro and in vivo

Zheng¹

2010

Oncol Rep

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Abstract. Urotensin II (UII), originally identified from fish urophysis, is a potent vasoactive peptide and an endogenous ligand for an orphan G protein-coupled receptor GPR14, now named as urotensin II receptor (UT-R). In this study, we investigated the mRNA and protein expressions of UII and its receptor (UT-R) in human lung adenocarcinoma A549 cells, and the effect of exogenous UII on the proliferation of A549 cells in vitro and in vivo. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis showed that both mRNAs and proteins of UII and UT-R were obviously expressed in human lung adenocarcinoma A549 cells. Immunohistochemical analysis showed that UII peptide was mainly expressed in the cytoplasm, and UT-R protein was expressed on the cytomembrane and also in the cytoplasm. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) analysis demonstrated that treatment with different concentrations of human UII (10 -9 , 10 -8 , 10 -7 and 10 -6 M) for 48 h significantly increased the number of A549 cells. The effect of UII at the concentration of 10 -7 M on the proliferation of A549 cells is most pronounced. Nude mice bearing human lung adenocarcinoma A549 cells treated with UII showed a significant increase in tumor volume and tumor weight compared with control group. These findings suggest that UII may contribute to the pathogenesis of human lung adenocarcinoma as an autocrine/paracrine growth stimulating factor.

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Expression and Functional Role of Urotensin-II and Its Receptor in the Adrenal Cortex and Medulla: Novel Insights for the Pathophysiology of Primary Aldosteronism

Abstract: Urotensin II is a putative mediator of the effects of the adrenal medulla and pheochromocytoma on the adrenocortical zona glomerulosa. This pathophysiological link might account for the reported causal relationship between pheochromocytoma and primary aldosteronism.

Cited by 27 publications

References 33 publications

Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

Role of urotensin II in health and disease

Expression of urotensin II and its receptor in human lung adenocarcinoma A549 cells and the effect of urotensin II on lung adenocarcinoma growth in vitro and in vivo

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