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.
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000698:Analgesia; D000818:Animals; D001921:Brain / Q000201:enzymology*; D055598:Chemical Phenomena; D002621:Chemistry; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D004743:Enkephalin, Leucine; C035766:leucinal; D000626:Aminopeptidases; D007930:Leucine