ENDOTHELIN-1 DOES NOT MODULATE O-2-CENTER-DOT RELEASE AND [CA2-60 CELLS(](I) VARIATIONS IN RESTING OR DIFFERENTIATED HL)

Endothelin-1 (ET-1) by itself was not an effective stimulus for induci ng superoxide (O-2 .) generation in human resting or DMSO-differentiat ed neutrophil-like HL-60 cells. ET-1 (0.01 - 100 nM) was not able to m odulate O-2 . generation stimulated by the chemotactic peptide N-formy l-L-methionyl-L-leucyl-L-phenylalanine (fMLP, EC(50) = 4.24 +/- 1.63 n M in the absence and 3.16 +/- 1.95 nM in the presence of ET-1). Neithe r did ET-1 (0.01 - 100 nM) promote the mobilization of intracellular c alcium ions or modulate fMLP-induced [Ca2+](i) increase in this model of human neutrophils. Phosphoramidon, a neutral endopeptidase inhibito r, was not able to reveal any biological (O-2 .) or biochemical ([Ca2](i)) response to ET-1 in the absence or in the presence of fMLP in th ese cells. These results indicate that DMSO-differentiated neutrophil- like HL-60 cells are not sensitive to ET-1 in terms of O-2 . generatio n or [Ca2+](i) variations.