β-Endorphin biotransformation in brain: Formation of γ-endorphin by a synaptosomal plasma membrane associated endopeptidase distinct from cathepsin D

Abstract

cSPM preparations of rat brain contain a peptidase activity which generates γ-endorphin from β-endorphin. Some properties of this enzyme were studied and compared with those of cathepsin D. Maximal accumulation of γ-endorphin upon digestion of β-endorphin with a cSPM preparation was found at neutral pH values. The activity of cathepsin D, forming γ-endorphin and β-LPH 78–91 was limited to acidic pH values. The SPM associated peptidase was not inhibited by the specific cathepsin D inhibitor pepstatin. The peptidase activity remained associated with SPM preparations, which were purified extensively by sucrose density centrifugation. It is concluded that the SPM associated peptidase which generates γ-endorphin from β-endorphin is distinct from cathepsin D. Such an enzyme may have a physiological function in the formation of β-endorphin fragments in the brain.