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Endothelin (ET-1) has been shown to exert vasoconstrictor activity in vivo and mobilize Ca2+ in vascular smooth muscle cells in culture. In this paper we show that the human skin fibroblast exhibits specific receptors to ET-1 and that activation of these receptors results in increased intracellular Ca2+ (Ca2+i) and accelerated Na+/H+ antiport activity. ET-1 raised Ca2+i in a dose-response manner; the peak Ca2+i rise was from basal levels of 112.2 +/- 21.9 to 299.2 +/- 49.7 nM at 300 nM ET-1. This rise was attenuated by removal of extracellular Ca2+i0. Although ET-1 did not alter basal intracellular pH, it enhanced Na+/H+ antiport activity of acidified cells. Fibroblasts demonstrated 156 +/- 18 (mean +/- SE) ET-1 receptors per unit cell and an equilibrium dissociation constant of 203.4 +/- 35.6 pM. Inasmuch as ET-1 plays a role in the metabolism of cells such as the undifferentiated fibroblast, an important action of this peptide may be to act as a growth factor.
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