Every lot is tried & tested in a relevant biological assay.
- Iglarz, M. et al. (2008) J. Pharmacol. Exp. Ther. 327, 736.
- Alomone Labs ACT-132577 inhibits ET-B receptor-mediated Ca2+ mobilization in CHO cells.Dose-response plot of ACT-132577 (#A-350) inhibition of the ET-B receptor-mediated, endothelin-1-evoked Ca2+ mobilization (IC50 = 5.99 µM). Cells were loaded with Calcium 6 dye, incubated with ACT-132577, and stimulated with 30 nM endothelin-1 (EC80). Changes in intracellular Ca2+ levels were detected as changes in maximum relative fluorescence (RLU) using FLIPRTETRA™.
ACT-132577 is an active metabolite of Macitentan that acts as an endothelin B (ET-B) and endothelin A (ET-A) receptor antagonist. ACT-132577 antagonizes the specific binding of endothelin-1 on membranes of cells overexpressing ET-A and ET-B receptors with IC50 values of 3.4 nM and 987 nM, respectively1. It also has the ability to reach full inhibition of intracellular Ca2+ increase induced by endothelin-1 on non-recombinant cells1.
Endothelin receptors belong to the superfamily of G-protein coupled receptors and include two subtypes: ET-A and ET-B. ET-A receptors are predominantly expressed in peripheral tissues, especially in vascular smooth muscle tissues to mediate vasoconstriction. They are also present in several different regions of the brain. ET-B receptors play an important role in regulating renal function and blood pressure and are expressed in sensory nerves. They are mainly detected in medium- and large-sized cell bodies of human trigeminal ganglia.
The ET-A receptor has high affinity for endothelin-1 and endothelin-2 and relatively low affinity for endothelin-3, while the ET-B receptor has high affinity for all endothelin isopeptides2,3.