StructureâFunction Analysis of Urotensin II and Its Use in the Construction of a LigandâReceptor Working Model

Kinney, William A.; Almond, Harold R.; Qi, Jenson; Smith, Charles E.; Santulli, Rosemary; Garavilla, Lawrence de; Andrade‐Gordon, Patricia; Cho, Daniel S.; Everson, Anita M.; Feinstein, Mark A.; Leung, Perry; Maryanoff, Bruce E.

doi:10.1002/1521-3773(20020816)41:16<2940::aid-anie2940>3.0.co;2-m

Cited by 82 publications

(112 citation statements)

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“…U-II is characterized by a disulfi de-linked C-terminal structure. The cyclic region of U-II, which confers biological activity, has been conserved in evolution from fi sh to mammals [19][20][21][22]. The N-terminus of the peptide is known to vary in length and sequence, giving species/isoform differences [22] ( Fig.…”

Section: Intracellular Signalling Pathwaysmentioning

confidence: 99%

Role of urotensin II and its receptor in health and disease

2007

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Urotensin II (U-II) is currently the most potent vasoconstrictor identified. This action is brought about via activation of a G(q/11)-protein coupled receptor (UT receptor). U-II activation of the UT receptor increases inositol phosphate turnover and intracellular Ca(2+). In addition to producing vasoconstriction, dilation and ionotropic effects have also been described. There is considerable variation in the responsiveness of particular vascular beds from the same and different species, including humans. Receptors for U-II are located peripherally on vascular smooth muscle (contractile responses) and endothelial cells (dilatory responses via nitric oxide). In humans, plasma U-II is elevated in heart failure, renal failure, liver disease, and diabetes. Iontophoresis of U-II in healthy volunteers produces vasodilation (of the forearm) while in patients with heart failure or hypertension a constriction is observed. To date there is only one clinical study using a UT receptor antagonist (palosuran) in diabetic patients with macroalbuminuria. This antagonist reduced albumin excretion, probably by increasing renal blood flow. Studies in other disease conditions are eagerly awaited. In summary, the U-II / UT receptor system has clinical potential, and for the anesthesiologist, this novel peptide-receptor system may be of use in the intensive care unit.

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Section: Intracellular Signalling Pathwaysmentioning

confidence: 99%

Role of urotensin II and its receptor in health and disease

2007

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“…These studies showed the importance of the side chains of the residues Trp7, Lys8, and Tyr9 for recognition and activation of the UT receptor [52][53][54][55]. A detailed investigation of these positions indicated that the replacement of the Trp7 residue with the corresponding D-isomer switches the activity from agonist to partial agonist [52][53][54][55][56]. Similarly, partial agonists are obtained by replacement of Lys8 residue with ornitine (Orn).…”

Section: Peptide Ut Receptor Antagonistsmentioning

confidence: 99%

“…All the reported compounds contain the following features: a basic amino group and, at least, two aromatic moieties. For peptide and non-peptide agonists [53,62], the basic amino group was shown to form a charged interaction with an Asp residue (D130 in hUT) within TM3 of the receptor.…”

Section: Non Peptide Ut Receptor Antagonistsmentioning

confidence: 99%

Urotensin-II Receptor Antagonists

Carotenuto

Grieco²,

Rovero³

et al. 2006

CMC

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Urotensin-II (U-II) is a "somatostatin-like" cyclic neuropeptide which was originally isolated from goby fish urophysis, and subsequently identified in other species, including man. The interest in human U-II (hU-II) has grown enormously in the last few years, following the identification of a specific human receptor (formerly identified as the GPR14/SENR orphan receptor), now referred to as UT receptor. The U-II/UT system seems to play an important role in cardiovascular functions. hU-II vasoconstrictive potency is reported to be an order of magnitude greater than that of endothelin-1 (ET-1), which would make it the most potent mammalian vasoconstrictor identified to date. hU-II also exerts potent inotropic effects in the human heart in vitro. On the basis of its spectrum of activities, hU-II has been suggested to modulate cardiovascular homeostasis and possibly to be involved in certain cardiovascular pathologies. Central nervous effects of U-II have also been described, in particular, intracerebroventricular administration promotes anxiogenic-like behaviors in rodents. Furthermore, UT receptor overexpression has been observed in some tumor cell lines. Therefore, specific and selective UT receptor antagonists provide useful tools for investigating the (patho)physiological role(s) of the U-II/UT receptor system. In this review we aim to provide an overview of the research in the area of UT receptor antagonists as well as the progress in understanding the role of the U-II/UT system in human (patho)physiology.

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“…Structure-activity relationship studies have shown that the cyclic C-terminal hexapeptide corresponds to the biologically active region of U-II (Flohr et al 2002;Kinney et al 2002;Labarrère et al 2003). Recently, a paralogue of U-II, termed U-IIrelated peptide (URP), has been isolated from the rat brain, and the cDNA encoding the URP precursor has been cloned in mice, rats, and humans (Sugo et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Behavioral effects of urotensin-II centrally administered in mice

do-Rego

Chatenet²,

Orta³

et al. 2005

Psychopharmacology

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Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.

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StructureâFunction Analysis of Urotensin II and Its Use in the Construction of a LigandâReceptor Working Model

Cited by 82 publications

References 3 publications

Role of urotensin II and its receptor in health and disease

Role of urotensin II and its receptor in health and disease

Urotensin-II Receptor Antagonists

Behavioral effects of urotensin-II centrally administered in mice

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StructureâFunction Analysis of Urotensin II and Its Use in the Construction of a LigandâReceptor Working Model

Cited by 82 publications

References 3 publications

Role of urotensin II and its receptor in health and disease

Role of urotensin II and its receptor in health and disease

Urotensin-II Receptor Antagonists

Behavioral effects of urotensin-II centrally administered in mice

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Product

Resources

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StructureâFunction Analysis of Urotensin II and Its Use in the Construction of a LigandâReceptor Working Model