A new ligand for the urotensin II receptor.
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.
Camarda
Valeria
V
Department of Experimental and Clinical Medicine, Section of Pharmacology, via Fossato di Mortara 17-19, Ferrara, 44100 Ferrara, Italy.
Guerrini
Remo
R
Kostenis
Evi
E
Rizzi
Anna
A
Calò
Girolamo
G
Hattenberger
Almut
A
Zucchini
Marina
M
Salvadori
Severo
S
Regoli
Domenico
D
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*
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