Effect of endothelin receptor antagonist, BQ-123, on Ca2+ signaling in cultured rat mesangial cells

Endothelin (ET)-1 causes mesangial cell contraction and proliferation. The present study was designed to evaluate the functional ET receptor subtype in cultured rat mesangial cells by measuring intracellular Ca2+ signaling with the use of a newly synthesized ET receptor type A selective antagonist-BQ123. The ET-1, ET-2 and ET-3 increased intracellular Ca2+ level in a dose-dependent manner. BQ-123 suppressed intracellular Ca2+ elevation in response to ET-1 in a dose-dependent manner with its half maximal inhibition value of 28 nM. BQ-123 (10(-6) M) did not affect ET-3 (10(-7) M)-induced Ca2+ response. The peak Ca2+ levels after addition of ET-3 without BQ-123 were similar to those in response to ET-1, ET-2 and ET-3 in the presence of BQ-123. Northern blot analysis showed that cultured mesangial cells expressed both ETA and ETB receptor mRNA. These results suggest that cultured mesangial cells have, at least, two types of functional receptors, one of which is an ETA receptor.