Human brain contains a metalloprotease that converts big endothelin‐1 to endothelin‐1 and is inhibited by phosphoramidon and EDTA

Abstract

Incubation of big endothelin‐1 (bET‐1) with protein derived from the detergent‐extracted 100,000 g pellet prepared from human brain tissue resulted in the formation of endothelin‐1 (ET‐1) at a rate of 90 fmol mg−1 protein min−1. This formation was inhibited in a concentration‐dependent manner by either phosphoramidon or EDTA, with half‐maximal inhibitory concentrations of 2 and 20 μm, respectively. No conversion of big endothelin‐3 (bET‐3) to endothelin‐3 (ET‐3) was detected under the same conditions. These results show the presence in the human brain of a metalloprotease‐like enzymatic activity which selectively converts bET‐1 and ET‐1. Together with earlier reports of mRNA for ET‐1 this suggests the presence of the entire synthetic pathway for ET‐1 in human brain. 1992 British Pharmacological Society