Inactivation of Neurotensin by Rat Brain Synaptic Membranes Partly Occurs Through Cleavage at the Arg8‐Arg9 Peptide Bond by a Metalloendopeptidase

Abstract

One of the primary inactivating cleavages of neurotensin (NT) by rat brain synaptic membranes occurs at the Arg⁸-Arg⁹ peptide bond, leading to the formation of NT_1-8 and NT^9-13. The involvement at this site of a recently purified metalloendopeptidase was demonstrated by the use of its specific inhibitor, N-[1(R,S)-carboxy-2-phenylethyl]-alanylalanylphenylalanine-p-aminobenzoate, which exerts an inhibition on NT_1-8 formation with an IC₅₀ (0.6 μM) close to its K_i for the purified metalloendopeptidase (1.94 μM). Furthermore, we established the role of a postproline dipeptidyl-aminopeptidase in the secondary processing of NT_9-13 formation.