Endothelin-2 is a peptide vasoconstrictor and ligand for the endothelin (ET) receptors ETA and ETB (Kbs= 32.8 and 1.33 nM, respectively).1 It induces β-arrestin recruitment in CHO-K1 cells expressing human ETA and ETB (pD2s =8.75 and 8.55, respectively). Ex vivo, endothelin-2 induces vformal asoconstriction in isolated rat mesenteric arterial beds (ED50 = 90.8 pmol).2 Endothelin-2 also induces contraction of isolated rat uteri, an effect which is reversed by the ETA antagonist BQ-123 but not the ETB antagonist BQ-788 .3 Infusion of endothelin-2 restores vasoconstriction of vessels at the follicular apex of the ovarian follicle and ovulation in Amhr2cre/+Smo2 mice.4
1.Maguire, J.J., Kuc, R.E., Pell, V.R., et al.Comparison of human ETA and ETB receptor signalling via G-protein and β-arrestin pathwaysLife Sci.91(13-14)544-549(2012) 2.Douglas, S.A., and Hiley, C.R.Endothelium-dependent vascular activities of endothelin-like peptides in the isolated superior mesenteric arterial bed of the ratBr. J. Pharmacol.101(1)81-88(1990) 3.Kousides, M., Story, M.E., and Pennefather, J.N.Endopeptidase 24.11 inhibition does not modify uterotonic effects of endothelins in rat uterusPeptides19(9)1585-1593(1998) 4.Migone, F.F., Cowan, R.G., Williams, R.M., et al.In vivo imaging reveals an essential role of vasoconstriction in rupture of the ovarian follicle at ovulationProc. Natl. Acad. Sci. USA113(8)2294-2299(2016)