Specificity of Action on Neuropeptides of an Endopeptidase from the Synaptosomal Membranes of Guinea Pig Brain1

An endopeptidase was solubilized and highly purified from the synaptosomal membrane fraction of guinea pig brain, and its specificity of action on various neuropeptides was investigated. It hydrolyzed specifically the Pro10-Tyr " bond of neurotensin and showed a marked specificity toward Pro-X bonds present in the interior parts of various neuropep-tides and related peptides. No cleavage, however, was observed at the first and second peptide bonds from the NH2-termini or from the COOH-termini of the peptides examined, suggesting that the enzyme requires both NH2- and COOH-terminal extentions of at least 3 residues from the scissile bond for its action. In addition, a limited number of other peptide bonds were cleaved, indicating that the enzyme is not strictly specific to Pro-X bonds. These results suggest the possible implication of this enzyme in the specific degradation of neurotensin and other peptide neurotransmitters in the synaptic cleft. Increasing numbers of neuropeptides are being discovered which are assumed to act as neurotransmitters or neuro-modulators in the nervous system. Most of the peptide neurotransmitters are thought to be enzymatically in