Degradation of substance P by neuronal and glial cells cultured from rat fetal brain and their membranes.

By HPLC analysis, neuronal and glial cells cultured from rat fetal brain and their membrane preparations were shown to degrade substance P (SP) added exogenously. The degradation by neuronal cells and their membranes resulted in marked accumulation of SP fragments (1-4) and (1-6), and the accumulation, as well as the initial cleavage of SP, was strongly inhibited by metal chelators but not by phosphoramidon and captopril. Proposed cleavage sites by neuronal cells were almost identical to those by a substance P-degrading endopeptidase previously purified from rat brain by us (J. Biochem. 104: 999-1006 (1988)). On the other hand, the action of glial cells and their membranes on SP produced the fragments (1-6), (1-4), (10-11) and (8-9) in high amounts. The production, as well as the initial cleavage of SP, was inhibited not only by metal chelators and p-chloromercuribenzenesulfonic acid but also by phosphoramidon. Proposed cleavage sites by glial cells were almost identical to those attacked by endopeptidase-24.11. Thus, the proteases that degrade SP in neuronal cells and glial cells seem different.