Degradation of dynorphin-(1-13) and dynorphin-(1-17) by the neuroblastoma cell membrane. Evidence for the involvement of a cysteine protease.

The membrane of mouse neuroblastoma N-18 cells degraded dynorphin-(1-13), dynorphin-(1-17), and Leu-enkephalin. The degradation of the former two peptides was inhibited strongly by N-ethylmaleimide, moderately by diisopropylphosphorofluoridate and phosphoramidon, and slightly by bestatin. When Leu-enkephalin was the substrate, however, the effects of phosphoramidon and bestatin were marked and those of N-ethylmaleimide and diisopropylphosphorofluoridate were negligibly small. Captopril did not affect the degradation of the two dynorphins and Leu-enkephalin, but inhibited the further cleavage of N-terminal fragments generated from dynorphin-(1-13) by the N-ethylmaleimide-sensitive protease. Thus, a cysteine protease and, probably, a serine protease are responsible to the initial fragmentation of the dynorphins.