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Nociceptin/Orphanin FQ Metabolism: Role of Aminopeptidase and Endopeptidase 24.15
Author(s) -
Montiel JoseLuis,
Cornille Fabrice,
Roques Bernard P.,
Noble Florence
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68010354.x
Subject(s) - nociceptin receptor , endopeptidase , enkephalin , chemistry , opioid peptide , neprilysin , aminopeptidase , neuropeptide , biochemistry , dynorphin , receptor , opioid , endocrinology , enzyme , biology , amino acid , leucine
The endogenous opioid receptor‐like 1 (ORL 1 ) ligand, nociceptin/orphanin FQ (FGGFTGARKSARKLANQ), a heptadecapeptide structurally resembling dynorphin A, has recently been identified. The wide distribution of ORL 1 mRNA and nociceptin/orphanin FQ precursor in the CNS, particularly in the limbic system regions and in several areas known to be involved in pain perception, suggests that nociceptin/orphanin FQ is potentially endowed with various central functions. In general, activation and/or inactivation of regulatory peptides occur through the action of cell surface peptidases. The physiological mechanisms under which nociceptin/orphanin FQ is metabolized should lead to a better understanding of its physiological functions. Mouse brain cortical slices were incubated in medium containing the heptadecapeptide in the presence or in the absence of peptidase inhibitors. The critical sites of enzymatic cleavage are Phe 1 ‐Gly 2 , Ala 7 ‐Arg 8 , Ala 11 ‐Arg 12 , and Arg 12 ‐Lys 13 bonds. The major role played by metallopeptidases was confirmed by the complete protection of metabolism in the presence of EDTA. Aminopeptidase N and endopeptidase 24.15 are the two main enzymes involved in nociceptin/orphanin FQ metabolism, whereas endopeptidase 24.11 (involved in enkephalin [YGGFM(L)] catabolism) does not appear critically involved in nociceptin/orphanin FQ metabolism. The physiological relevance of aminopeptidase N and endopeptidase 24.15 in the heptadecapeptide metabolism remains to be determined.