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Association of aminopeptidase N and endopeptidase 24.15 inhibitors potentiate behavioral effects mediated by nociceptin/orphanin FQ in mice
Author(s) -
Noble Florence,
Roques Bernard P
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01476-7
Subject(s) - nociceptin receptor , chemistry , nop , in vivo , opioid peptide , receptor , endopeptidase , endogeny , aminopeptidase , opioid , pharmacology , endocrinology , medicine , biochemistry , enzyme , biology , amino acid , leucine , microbiology and biotechnology
The behavioral effects induced by central administration in mice of the endogenous ORL 1 (opioid receptor‐like 1 ) 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(PO 2 CH 2 )( 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(PO 2 CH 2 )( 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.