Dipeptidase activities in rat brain synaptosomes can be distinguished on the basis of inhibition by bestatin and amastatin : identification of a kyotorphin (Tyr-Arg)-degrading enzyme

• Published in: Neurochemical research Vol. 17; no. 8; pp. 817 - 820
• Main Authors: ORAWSKI, A. T, SIMMONS, W. H
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-08-1992
• Subjects: Animals; Anti-Bacterial Agents; Biochemistry and metabolism; Biological and medical sciences; Brain - enzymology; Central nervous system; Chromatography, Gel; Detergents; Dipeptidases - antagonists & inhibitors; Dipeptidases - metabolism; Endorphins - metabolism; Fundamental and applied biological sciences. Psychology; Leucine - analogs & derivatives; Leucine - pharmacology; Oligopeptides - pharmacology; Peptides; Rats; Rats, Inbred Strains; Substrate Specificity; Synaptosomes - enzymology; Vertebrates: nervous system and sense organs; Vertebrata; Dipeptidase; Synaptosome; Mammalia; Enzymatic activity; Rat; Enzyme; Rodentia; Central nervous system; Neuropeptide; Brain (vertebrata)
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/bf00969018

The neuropeptide kyotorphin (Tyr-Arg) was degraded by rat brain synaptosomes via a synaptic membrane-bound peptidase which was inhibited by bestatin but not by amastatin. The Km for kyotorphin was 8 x 10(-6) M and the Ki for bestatin was 1 x 10(-7) M. The kyotorphin-degrading enzyme was distinguished from at least one other dipeptide-hydrolyzing activity in synaptosomes which was inhibited by both bestatin and amastatin. Gel permeation chromatography of detergent-extracted synaptosomes resulted in the separation of the dipeptide-hydrolyzing activities. A single kyotorphin-degrading enzyme peak was observed which had a M(r) = 52,000. The activity peak could degrade other dipeptides including Phe-Arg, a synaptic membrane-generated metabolic of bradykinin. The kyotorphin-degrading enzyme appears to be novel and can be distinguished from other known dipeptidases on the basis of substrate specificity, subcellular localization, and inhibition profile.