Biological activity of the endothelin family in cultured basilar arterial smooth muscle cells.

The effects of three forms of endothelin (ET), ET-1, -2 and -3, on intracellular free Ca2+ concentration ([Ca2+]i), their receptor binding activities, and DNA synthesis were investigated in cultured porcine basilar arterial smooth muscle cells. Endothelin-1 and ET-2 induced cytosolic free calcium elevations that did not return to the basal level. The maximum levels of [Ca2+]i induced by the three points were ET-1 approximately equal to ET-2 > ET-3. The cells display specific binding of 125I-labelled endothelin-1 which was displaced by three endothelins; ET-1, -2, and -3, in a concentration-dependent manner. The order of potency in inhibiting 125I-labeled endothelin-1 binding was ET-1 approximately equal to ET-2 > ET-3. Endothelin-1, ET-2, and ET-3 stimulated [3H]thymidine incorporation in a dose-dependent manner, the maximum order of potency (100 nM) was again ET-1 approximately equal to ET-2 > ET-3. These results indicate that ET-1 and ET-2 are more potent in their biological activities than ET-3 in cultured cerebral arterial smooth muscle cells.