Characterization of rat prepro-orphanin FQ/nociceptin((154-181)): nociceptive processing in supraspinal sites.
Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the orphan receptor-like/kappa(3)-like opioid receptor clone, produces a variety of behavioral responses, including those associated with pronociception and antinociception. The OFQ/N precursor rattus-proOFQ (rppOFQ/N) contains several paired basic amino acids, which raises the possibility that post-translational processing can be responsible for the production of a number of additional biologically active peptide fragments. One of these putative peptides, rppOFQ/N (rppOFQ/N(154-181)), was examined for antinociceptive and pronociceptive processes in four brain sites involved in pain inhibition: the ventrolateral periaqueductal gray (vlPAG), the amygdala, the locus coeruleus (LC), and the rostroventromedial medulla (RVM). Endogenous rppOFQ/N(154-181) was identified in each region. rppOFQ/N(154-181) produced a dose-dependent antinociception in all four sites using the tailflick assay. Injections into misplaced cannula sites failed to exert effects. Antinociception in the four sites differed in their response to the opioid antagonist naloxone. Naloxone pretreatment completely blocked rppOFQ/N(154-181)-induced antinociception in the vlPAG and the amygdala, but not in the LC or RVM. In contrast rppOFQ/N(154-181) was hyperalgesic in the LC and RVM, but not in the vlPAG or amygdala. rppOFQ/N(154-181) also was compared with either its N-terminal 17-amino acid peptide (rppOFQ/N(154-170), also known as OFQ2) or its 8-amino acid C-terminal fragment (rppOFQ/N(174-181)). Although both rppOFQ/N(154-181) and rppOFQ/N(154-170) produced antinociception, the latter was less effective because the C-terminal fragment was inactive. Thus, rppOFQ/N(154-181) has complex antinociceptive and pronociceptive actions within the brain, and the pharmacological specificity of its actions differs among supraspinal sites.
Rossi
Grace C
GC
Long Island University, Brookville, New York 11548, USA. grossi@liu.edu
Pellegrino
Michael
M
Shane
Randi
R
Abbadie
Catherine A
CA
Dustman
Jessica
J
Jimenez
Charles
C
Bodnar
Richard J
RJ
Pasternak
Gavril W
GW
Allen
Richard G
RG
D000679:Amygdala / Q000187:drug effects; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D018847:Opioid Peptides / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; C444646:prepro-orphanin FQ (154-181); D009270:Naloxone