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A new ligand for the urotensin II receptor
Author(s) -
Camarda Valeria,
Guerrini Remo,
Kostenis Evi,
Rizzi Anna,
Calò Girolamo,
Hattenberger Almut,
Zucchini Marina,
Salvadori Severo,
Regoli Domenico
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704895
Subject(s) - agonist , receptor , urotensin ii , g protein coupled receptor , ligand (biochemistry) , partial agonist , antagonist , pharmacology , chemistry , hek 293 cells , medicine , endogenous agonist , biology , endocrinology , biochemistry , dopamine receptor d1
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 ≈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. British Journal of Pharmacology (2002) 137 , 311–314. doi: 10.1038/sj.bjp.0704895