Noble F, Roques B P
Département de Pharmacochimie Moléculaire et Structurale, INSERM U266-CNRS URA D 1500, Université René Descartes, Paris, France.
FEBS Lett. 1997 Jan 20;401(2-3):227-9. doi: 10.1016/s0014-5793(96)01476-7.
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.
在内源性阿片样物质受体1（ORL1）配体——孤啡肽/痛敏肽对小鼠进行中枢给药所诱导的行为效应，是在不存在或存在氨肽酶N抑制剂（苯丁抑制素）和内肽酶24.15抑制剂（Z-(L,D)苯丙氨酸ψ(PO2CH2)(L,D)丙氨酸-精氨酸-苯丙氨酸）的情况下进行研究的，最近的研究表明这些酶在体外参与了十七肽的代谢。在两项测试（自发运动活性和旷场试验）中测量了孤啡肽/痛敏肽所诱导的运动活性的显著降低。苯丁抑制素和Z-(L,D)苯丙氨酸ψ(PO2CH2)(L,D)丙氨酸-精氨酸-苯丙氨酸联用可增强这种药理效应，从而在体内证实了这些肽酶参与孤啡肽/痛敏肽的失活。在我们的实验条件下，这些抑制剂没有内在效应，这表明十七肽对所测量行为的紧张性调节作用较低。
