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 +/- 70.32 (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.