beta-Endorphin is converted into the biologically active fragment gamma-endorphin by an endopeptidase which we term "gamma-endorphin generating endopeptidase". Subcellular and regional distributions of this endopeptidase activity in rat brain were studied by a newly developed assay. After subcellular fractionation of rat brain tissue gamma-endorphin generating endopeptidase activity was predominantly recovered in the cytosolic fraction. A 10 to 15 fold lower activity was present in synaptosomes, mitochondria and synaptic membranes. Hardly any endopeptidase activity was detected in nuclei and myelin. The endopeptidase activity in cytosolic and particulate fraction was found throughout brain, pituitary and spinal cord in a rather homogeneous fashion. Cytosolic activity in all brain parts was 10 to 15 fold higher than the activity in the particulate fraction. It is suggested that rather the beta-endorphin distribution than the endopeptidase is restricting for gamma-endorphin production in certain brain parts.
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