Metabolism of endothelin-1 by neuroblastoma x glioma hybrid (NG108-15) cells

The endothelin (ET) peptides, ET-1, ET-2, and ET-3, as well as the ET(A) and ET(B) receptor subtypes, are known to occur in brain, but there is a dearth of information on the metabolism of these peptides by the central nervous system (CNS). In this study we have investigated the kinetics of ET-1 binding to and dissociation from the hybrid neuroblastoma x glioma cell line, NG108-15, which is known to contain functional ET receptors, and metabolism of bound ET-1. [¹²⁵I]ET-1 was incubated with cells for various periods of time up to 6 h, and the nature of the radioactivity in the cell medium and lysate was analyzed by reverse phase high performance liquid chromatography (HPLC). It was found that NG108-15 cells are capable of degrading [¹²⁵I]ET-1 to [¹²⁵I]Tyr and several fragments of intermediate hydrophobicity; however, a portion of the cell-associated [¹²⁵I]ET-1 was protected from degradation for several hours.