Leucinal inhibits brain aminopeptidase activity and potentiates analgesia induced by leu-enkephalen

L-Leucinal, a transition state analog inhibitor or kidney leucine amino-peptidases, was found to serve as a competitive inhibitor of soluble aminopeptidase activity from rat brain (Ki = 22 microM). Simultaneous intracisternal administration of leucinal and leu-enkephalin produced dose-dependent analgesia in the hot plate test in mice, in concentrations at which neither L-leucinal nor leu-enkephalin alone elicited a significant response. simultaneous administration of leucinal and beta-endorphin also resulted in potentiation of beta-endorphin's analgesic activity. Leucinal did not enhance the antinociceptive response to neurotensin or to [D-ala2]-met-enkephalinamide, which are structurally resistant to the action of brain aminopeptidases.