DEGRADATION OF ENDOTHELIN-1 BY EXTRACTS OF RAT LUNG, KIDNEY, AND LIVER

Degradation of I-125-labeled endothelin-1 (I-125-ET-1) when incubated 120 min at 37 degrees C with rat lung, kidney and liver plasma membran e extracts was examined using HPLC. Lung and kidney extracts showed de grading enzyme activity, but none was found in liver extract. EDTA. al most abolished degradation of I-125-ET-1 in lung and kidney extracts. Phosphoramidon and SCH 39370, both inhibitors of neutral endopeptidase 24.11 (NEP), markedly inhibited degradation of I-125-ET-I in lung ext ract and clearly less in kidney extract. Soybean trypsin inhibitor (ST I) acid elastase inhibitor partly inhibited degradation in lungs and i n kidney extract. Leupeptin had no inhibitory effect neither in lung n or in kidney extract. Our results suggest: (1) at least two types of e nzymes degrade ET-1 in lung and kidney extracts, namely metalloprotein ases and serine proteinases. (2) The ET-1 degrading effect appears to be different in lungs and kidneys, metalloproteinases being more impor tant in pulmonary than in renal degradation of ET-1.