Autoradiographic localization of I-125[Tyr(14)]orphanin FQ/nociceptin and I-125[Tyr(10)]orphanin FQ/nociceptin(1-11) binding sites in rat brain

The endogenous ligand for the orphan opioid receptor, orphanin FQ/nocicepti n (OFQ), has recently been characterized. The OFQ peptide sequence contains paired basic amino acids, suggesting the possibility of posttranslational processing to a peptide containing the first 11 amino acids of the OFQ pept ide. This peptide has been reported in the brain and it has a unique pharma cology. In the present study, we compared the autoradiographic distribution of I-125[Tyr(14)] OFQ and I-125[Tyr(10)]OFQ(1-11) in coronal rat brain sec tions. Nonspecific binding was defined with unlabeled OFQ or OFQ(1-11), res pectively. Both radioligands demonstrated high levels of specific binding ( >95% of total binding), with no appreciable binding in white matter areas w ith either ligand. I-125[Tyr(14)]OFQ binding was widely distributed through out the rat brain. In contrast, I-125[Tyr(10)]OFQ(1-11) binding was more re stricted. The highest I-125[Tyr(14)]OFQ binding levels measured in this stu dy were found in the locus coeruleus, an area which contained very low I-12 5[Tyr(10)]OFQ(1-11) binding. Both ligands labeled the cortex, hippocampus a nd amygdala. In the thalamus, I-125[Tyr(14)]OFQ binding was prominent in mo st nuclei, whereas I-125[Tyr(10)] OFQ(1-11) binding was restricted to the m idline thalamus. I-125[Tyr(14)]OFQ binding was heavy in the suprachiasmatic hypothalamus, and moderate in other hypothalamic nuclei. I-125[Tyr(10)]OFQ (1-11) binding in the hypothalamus, however, was present mainly in the vent romedial hypothalamic nucleus. Lower binding levels of both ligands were fo und in the caudate putamen. The distinct autoradiographic patterns of these two ligands are consistent with different binding sites, which might help explain their different functional activities. J. Comp. Neurol. 423:319-329 , 2000. (C) 2000 Wiley-Liss, Inc.