title: A new ligand for the urotensin II receptor.
abstract: The cyclic peptide human urotensin II (U-II) has been recently recognized as the endogenous ligand of an orphan GPCR, subsequently named the UT receptor. No synthetic ligands are available for investigating this novel peptide-receptor system. A novel UT receptor ligand, [Orn(8)]U-II, was synthesized and evaluated in calcium functional assays performed on HEK293 cells expressing the recombinant rat and human UT receptor and in the rat aorta bioassay. [Orn(8)]U-II behaves as a full agonist (pEC(50) approximately equal 8) at both human and rat UT receptors in the FlipR calcium assay eliciting similar maximal effects as the natural ligand U-II. On the contrary, in the rat aorta bioassay, [Orn(8)]U-II behaves as a competitive and selective antagonist (pA(2)=6.56) showing however a small but consistent residual agonist activity. It is therefore proposed that [Orn(8)]U-II is a partial agonist at UT receptors.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Pharmacology, via Fossato di Mortara 17-19, Ferrara, 44100 Ferrara, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Camarda
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Evi
authors.initials: E
authors.lastname: Kostenis
authors.forename: Anna
authors.initials: A
authors.lastname: Rizzi
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calò
authors.forename: Almut
authors.initials: A
authors.lastname: Hattenberger
authors.forename: Marina
authors.initials: M
authors.lastname: Zucchini
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: C473469:(Orn8)urotensin-II; D008024:Ligands; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II; D002118:Calcium