Carboxyl terminal peptides derived from prepro-orphanin FQ/nociceptin (ppOFQ/N) are produced in the hypothalamus and possess analgesic bioactivities Journal Article

  

Authors:	Mathis, J. P.; Rossi, G. C.; Pellegrino, M. J.; Jimenez, C.; Pasternak, G. W.; Allen, R. G.
Article Title:	Carboxyl terminal peptides derived from prepro-orphanin FQ/nociceptin (ppOFQ/N) are produced in the hypothalamus and possess analgesic bioactivities
Abstract:	Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the ORL-1/KOR-3 receptor, produces a wide variety of behavioral responses. Its precursor protein, prepro-OFQ/N (ppOFQ/N) contains several series of amino acids bounded by pairs of basic amino acids. raising the possibility that additional functional neuropeptides could be generated by proteolytic posttranslational processing. Several of these processing products have been shown to have pharmacological activity, including the 17 amino acid peptide OFQ/N (mppOFQ/N140-157) which is a major product of this precursor in the hypothalamus. Here wt: have used a newly developed radioimmunoassay and RP-HPLC to detect mppOFQ/N160-187 in mouse hypothalamic extracts, Murine ppOFQ/N160-187 has potent analgesic activity supraspinally (3.3 nmol, i.c.v,) and spinally (4.3 nmol, i.t.). This analgesic activity was reversed by the opioid antagonist naloxone (5 mg/kg, s.c.) and kappa(1)-selective opioid antagonist nor-BNI (60 mug. i.c.v.), despite the inability of ppOFQ/N160-187 to compete binding in mu, delta, kappa(1), kappa(3). or OFQ/N binding assays. These findings suggest that murine ppOFQ/N160-187 may be a physiologically relevant neuropeptide with a novel mechanism of action. (C) 2001 Elsevier Science B.V. All rights reserved.
Keywords:	mice; receptor; precursor; nociceptin; mouse-brain; peptide processing; orl1; fq; ofq2
Journal Title:	Brain Research
Volume:	895
Issue:	1-2
ISSN:	0006-8993
Publisher:	Elsevier Science, Inc.
Date Published:	2001-03-23
Start Page:	89
End Page:	94
Language:	English
ACCESSION:	WOS:000167742400012
DOI:	10.1016/s0006-8993(01)02035-2
PROVIDER:	wos
PUBMED:	11259764
Notes:	Article -- Source: Wos

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