TY - JOUR T1 - Characterization of Rat Prepro-Orphanin FQ/Nociceptin<sub>(154–181)</sub>: Nociceptive Processing in Supraspinal Sites JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 257 LP - 264 DO - 10.1124/jpet.300.1.257 VL - 300 IS - 1 AU - Grace C. Rossi AU - Michael Pellegrino AU - Randi Shane AU - Catherine A. Abbadie AU - Jessica Dustman AU - Charles Jimenez AU - Richard J. Bodnar AU - Gavril W. Pasternak AU - Richard G. Allen Y1 - 2002/01/01 UR - http://jpet.aspetjournals.org/content/300/1/257.abstract N2 - Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the orphan receptor-like/κ3-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/N154–181), 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/N154–181 was identified in each region. rppOFQ/N154–181 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/N154–181-induced antinociception in the vlPAG and the amygdala, but not in the LC or RVM. In contrast rppOFQ/N154–181 was hyperalgesic in the LC and RVM, but not in the vlPAG or amygdala. rppOFQ/N154–181 also was compared with either its N-terminal 17-amino acid peptide (rppOFQ/N154–170, also known as OFQ2) or its 8-amino acid C-terminal fragment (rppOFQ/N174–181). Although both rppOFQ/N154–181 and rppOFQ/N154–170 produced antinociception, the latter was less effective because the C-terminal fragment was inactive. Thus, rppOFQ/N154–181 has complex antinociceptive and pronociceptive actions within the brain, and the pharmacological specificity of its actions differs among supraspinal sites. rppOFQ/Nrattus prepro-orphanin FQ/nociceptinrppOFQ/N154–181rattus prepro-orphanin FQ/nociceptin full-length peptideOFQ2prepro-orphanin FQ/N154–170 or beginning of full-length peptiderppOFQ/N174–181end of full-length peptidevlPAGventrolateral periaqueductal grayPAGperiaqueductal grayLClocus coeruleusRVMrostroventromedial medullaicvintracerebroventricularlyRP-HPLCreverse phase-high-performance liquid chromatography ER -