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 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.

British Journal of Pharmacology (2003) 139, 203–207. doi:10.1038/sj.bjp.0705251

DOI: 10.1038/sj.bjp.0705251

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