The neuromedin B receptor antagonist BIM-23127 is a potent antagonist at human and rat urotensin-II receptors

摘要

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 pEC50 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 (pA2=7.54±0.14; n=3) and rUT (pA2=7.70±0.05; n=3) receptors. Furthermore, BIM-23127 reversed hU-II-induced contractile tone in the rat-isolated aorta with a pIC50 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.