Inactivation of Neurotensin by Rat Brain Synaptic Membranes. Cleavage at the Pro10‐Tyr11 Bond by Endopeptidase 24.11 (Enkephalinase) and a Peptidase Different from Proline‐Endopeptidase

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Abstract
The tridecapeptide neurotensin is inactivated by rat brain synaptic membranes and one of the primary inactivating cleavages occurs at the Pro10-Tyr11 peptide bond, leading to the formation of NT1-10 and NT11-13. The possibility that this cleavage was catalyzed by proline endopeptidase and/or endopeptidase 24.11 (enkephalinase) was investigated. Purified rat brain synaptic membranes contained an N-benzyloxycarbonyl-Gly-Pro-4-methyl-coumarinyl-7-amide-hydrolyzing activity that was markedly inhibited (93%) by the proline endopeptidase inhibitor N-benzyloxycarbonyl-Pro-Prolinal and partially blocked (25%) by an antiproline endopeptidase antiserum. The cleavage of neurotensin at the Pro10-Tyr11 bond by synaptic membranes was not affected by N-benzyloxycarbonyl-Pro-Prolinal and the antiserum. When the conversion of NT1-10 to NT1-8 by angiotensin converting enzyme was blocked by captopril and when the processing of NT11-13 by aminopeptidase(s) was inhibited by bestatin, thiorphan, a potent endopeptidase 24.11 inhibitor, partially decreased the formation of NT1-10 and NT11-13 by synaptic membranes. Proline endopeptidase, although it is present in synaptic membranes, is not involved in the cleavage of neurotensin at the Pro10-Tyr11 bond. Endopeptidase 24.11 only partially contributes to this cleavage. There exists in rat brain synaptic membranes a peptidase different from proline endopeptidase and endopeptidase 24.11 that is mainly responsible for inactivating neurotensin by cleaving at the Pro10-Tyr11 bond.