The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensin-II receptors.
The functional activity of the peptidic neuromedin B receptor antagonist BIM-23127 was investigated at recombinant and native urotensin-II receptors (UT receptors). Human urotensin-II (hU-II) promoted intracellular calcium mobilization in HEK293 cells expressing the human UT (hUT) or rat UT (rUT) receptors with pEC(50) values of 9.80+/-0.34 (n=6) and 9.06+/-0.32 (n=4), respectively. While BIM-23127 alone had no effect on calcium responses in either cell line, it was a potent and competitive antagonist at both hUT (pA(2)=7.54+/-0.14; n=3) and rUT (pA(2)=7.70+/-0.05; n=3) receptors. Furthermore, BIM-23127 reversed hU-II-induced contractile tone in the rat-isolated aorta with a pIC(50) of 6.66+/-0.04 (n=4). In conclusion, BIM- 23127 is the first hUT receptor antagonist identified to date and should not be considered as a selective neuromedin B receptor antagonist.
Herold
Christopher L
CL
Cardiovascular and Urogenital Centre of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, PA 19406-0939, USA. heroldc1@yahoo.com
Behm
David J
DJ
Buckley
Peter T
PT
Foley
James J
JJ
Wixted
William E
WE
Sarau
Henry M
HM
Douglas
Stephen A
SA
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D014579:Urotensins / Q000494:pharmacology
C092829:BIM 23127; D010456:Peptides, Cyclic; D018004:Receptors, Bombesin; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C473142:Uts2r protein, rat; C029677:urotensin II; D002118:Calcium