The endothelin family of peptides are potent vasoconstrictors synthesized by endothelial cells in both constitutive and inducible pathways. The biological actions of endothelins are mediated by two GPCRs, ETA and ETB (Davenport, 2002). Whereas ETA is the predominant receptor on smooth muscle cells and thus is the primary mediator of the vasoconstrictor activity, ETB is found on endothelial cells and mediates vasodilation (Nilsson et al., 1997). In addition, ETB has also been linked to renal failure, congestive heart failure, atherosclerosis, and pulmonary hypertension (D'Orléans-Juste, et al., 2002). A mutation in ETB has been found to cause Hirschsprung disease-2, a degenerative disease of the digestive tract (Puffenberger et al, 1994). Cloned human ETB-expressing cell line is made in the CHO host, which supports high levels of recombinant ETB expression on the cell surface for functional detection via the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for agonists, antagonists, and modulators at ETB.