Endothelins inhibit adenylate cyclase in brain capillary endothelial cells.

The action of endothelins (Et) on cAMP formation was studied in endothelial cells from rat brain microvessels. Et-1 and Et-3 had no action by themselves. They both inhibited cholera toxin stimulated adenylate cyclase by about 50%. K0.5 values were observed at 2 nM and 40 nM for Et-1 and Et-3 respectively, indicating an involvement of a low affinity Et-3 receptor. Coupling to adenylate cyclase was achieved by a pertussis toxin sensitive mechanism. Another action of endothelins in brain capillary endothelial cells was to stimulate phospholipase C. This action involved a low affinity Et-3 receptor and a pertussis toxin insensitive mechanism. It is concluded that in brain capillary endothelial cells, ETA like receptors are coupled to phospholipase C and to adenylate cyclase via two different mechanisms.