Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors.
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 ([Pen5,DTrp7,Orn8]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 (CHO(hUT)). Indeed, urantide behaves as a competitive, potent (pA2 8.24), and pure antagonist in the rat aorta bioassay, while as an agonist (pEC50 8.11) in a calcium mobilization assay performed in CHO(hUT) cells. Urantide should be considered a low efficacy partial agonist.
Camarda
Valeria
V
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara, 19, 44100 Ferrara, Italy.
Song
Wei
W
Marzola
Erika
E
Spagnol
Martina
M
Guerrini
Remo
R
Salvadori
Severo
S
Regoli
Domenico
D
Thompson
Jonathan P
JP
Rowbotham
David J
DJ
Behm
David J
DJ
Douglas
Stephen A
SA
Calo'
Girolamo
G
Lambert
David G
DG
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004274:DNA, Recombinant / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D014579:Urotensins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D004274:DNA, Recombinant; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C029677:urotensin II; D002118:Calcium