Association of aminopeptidase N and endopeptidase 24.15 inhibitors potentiate behavioral effects mediated by nociceptin/orphanin FQ in mice.
The behavioral effects induced by central administration in mice of the endogenous ORL1 (opioid receptor-like1) ligand, nociceptin/orphanin FQ, were investigated in the absence or presence of inhibitors of aminopeptidase N (bestatin) and endopeptidase 24.15 (Z-(L,D)Phe psi(PO2CH2)(L,D)Ala-Arg-Phe) recently shown to be involved in the metabolism of the heptadecapeptide in vitro. A severe reduction in motor activity induced by nociceptin/orphanin FQ was measured in two tests (spontaneous motor activity and open field). This pharmacological effect was shown to be potentiated by the association of bestatin and Z-(L,D)Phe psi(PO2CH2)(L,D)Ala-Arg-Phe, confirming in vivo the involvement of these peptidases in nociceptin/orphanin FQ inactivation. In our conditions, these inhibitors were devoid of intrinsic effects, suggesting a low tonic regulation by the heptadecapeptide of the measured behaviour.
Noble
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Département de Pharmacochimie Moléculaire et Structurale, INSERM U266-CNRS URA D 1500, Université René Descartes, Paris, France.
Roques
B P
BP
D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018847:Opioid Peptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists*; D000097629:Nociceptin
D018826:CD13 Antigens; D004791:Enzyme Inhibitors; D007930:Leucine; D008666:Metalloendopeptidases; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C022510:thimet oligopeptidase; C012211:ubenimex