Degradation of endothelin-1 by extracts of rat lung, kidney, and liver

Abstract Degradation of 125 I-labeled endothelin-1 ( 125 I-ET-1) when incubated 120 min at 37°C with rat lung, kidney and liver plasma membrane extracts was examined using HPLC. Lung and kidney extracts showed degrading enzyme activity, but none was found in liver extract. EDTA almost abolished degradation of 125 I-ET-1 in lung and kidney extracts. Phosphoramidon and SCH 39370, both inhibitors of neutral endopeptidase 24.11 (NEP), markedly inhibited degradation of 125 I-ET-I in lung extract and clearly less in kidney extract. Soybean trypsin inhibitor (STI) and elastase inhibitor partly inhibited degradation in lungs and in kidney extract. Leupeptin had no inhibitory effect neither in lung nor in kidney extract. Our results suggest: (1) at least two types of enzymes degrade ET-1 in lung and kidney extracts, namely metalloproteinases and serine proteinases. (2) The ET-1 degrading effect appears to be different in lungs and kidneys, metalloproteinases being more important in pulmonary than in renal degradation of ET-1.