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

被引：56

作者：

Camarda, V

Song, W

Marzola, E

Spagnol, M

Guerrini, R

Salvadori, S

Regoli, D

Thompson, JP

Rowbotham, DJ

Behm, DJ

Douglas, SA

Calo, G

Lambert, DG

机构：

[1] Univ Ferrara, Pharmacol Sect, Dept Expt & Clin Med, I-44100 Ferrara, Italy

[2] Univ Leicester, Dept Cardiovasc Sci, Pharmacol & Therapeut Grp, Div Anaesthesia, Leicester LE1 7RH, Leics, England

[3] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy

[4] GlaxoSmithKline, Cardiovasc & Urogenital Ctr Excellence Drug Disco, King Of Prussia, PA USA

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2004年 / 498卷 / 1-3期

关键词：

urotensin-II; urantide; UT receptor; Ca2+; CHO cell; aorta; rat;

D O I：

10.1016/j.ejphar.2004.07.089

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Urotensin-II is the natural ligand of the UT receptor. This novel system is involved in the regulation of cardiovascular functions. Recently, a urotensin-II analog ([Pen(5),DTrp(7),Orn(8)]urotensin-II(4-11)) named urantide, has been proposed as a selective and potent UT receptor antagonist. In order to pharmacologically characterize this new compound, urantide was tested on the native UT receptors of the rat aorta and on the human recombinant receptors expressed in CHO cells (CHOuUT). Indeed, urantide behaves as a competitive, potent (pA(2) 8.24), and pure antagonist in the rat aorta bioassay, while as an agonist (pEC(50) 8.11) in a calcium mobilization assay performed in CHO,,UT cells. Urantide should be considered a low efficacy partial agonist. (C) 2004 Elsevier B.V. All rights reserved.

引用

页码：83 / 86

页数：4

共 17 条

[1] Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 [J].

Ames, RS ;

Sarau, HM ;

Chambers, JK ;

Willette, RN ;

Alyar, NV ;

Romanic, AM ;

Louden, CS ;

Foley, JJ ;

Sauermelch, CF ;

Coatney, RW ;

Ao, ZH ;

Disa, J ;

Holmes, SD ;

Stadel, JM ;

Martin, JD ;

Liu, WS ;

Glover, GI ;

Wilson, S ;

McNulty, DE ;

Ellis, CE ;

Elshourbagy, NA ;

Shabon, U ;

Trill, JJ ;

Hay, DWP ;

Ohlstein, EH ;

Bergsma, DJ ;

Douglas, SA .

NATURE, 1999, 401 (6750) :282-286

[2]

BERN HA, 1969, J ENDOCRINOL, V45, pR11

[3] Functional and binding characterizations of urotensin II-related peptides in human and rat urotensin II-receptor assay [J].

Brkovic, A ;

Hattenberger, A ;

Kostenis, E ;

Klabunde, T ;

Flohr, S ;

Kurz, M ;

Bourgault, S ;

Fournier, A .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 306 (03) :1200-1209

[4] A new ligand for the urotensin II receptor [J].

Camarda, V ;

Guerrini, R ;

Kostenis, E ;

Rizzi, A ;

Calò, G ;

Hattenberger, A ;

Zucchini, M ;

Salvadori, S ;

Regoli, D .

BRITISH JOURNAL OF PHARMACOLOGY, 2002, 137 (03) :311-314

[5]

CAMARDA V, 2004, THESIS U FERRERA FER

[6] From 'gills to pills': urotensin-II as a regulator of mammalian cardiorenal function [J].

Douglas, SA ;

Dhanak, D ;

Johns, DG .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2004, 25 (02) :76-85

[7]

DOUGLAS SA, 2000, IUPHAR COMPENDIUM RE, P365

[8] Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II [J].

Flohr, S ;

Kurz, M ;

Kostenis, E ;

Brkovich, A ;

Fournier, A ;

Klabunde, T .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (09) :1799-1805

[9] Central effects of urotensin-II following ICV administration in rats [J].

Gartlon, J ;

Parker, F ;

Harrison, DC ;

Douglas, SA ;

Ashmeade, TE ;

Riley, GJ ;

Hughes, ZA ;

Taylor, SG ;

Munton, RP ;

Hagan, JJ ;

Hunter, JA ;

Jones, DNC .

PSYCHOPHARMACOLOGY, 2001, 155 (04) :426-433

[10] A new, potent urotensin II receptor peptide agonist containing a pen residue at the disulfide bridge [J].

Grieco, P ;

Carotenuto, A ;

Campiglia, P ;

Zampelli, E ;

Patacchini, R ;

Maggi, CA ;

Novellino, E ;

Rovero, P .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (20) :4391-4394

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