Association of aminopeptidase N and endopeptidase 24.15 inhibitors potentiate behavioral effects mediated by nociceptin/orphanin FQ in mice

FEBS Letters

Noble, Florence¹  Roques, Bernard P¹ 

[1] Département de Pharmacochimie Moléculaire et Structurale, INSERM U266-CNRS URA D 1500, Université René Descartes, UFR des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, 75270 Paris Cedex 06, France

关键词: Nociceptin/orphanin FQ;    Metabolism;    Selective inhibitor;    Aminopeptidase N;    Endopeptidase-24.15;    Motor activity;    Open field;   

DOI  :  10.1016/S0014-5793(96)01476-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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)PheΨ(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)PheΨ(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.

【 授权许可】

Unknown