Autoradiographic localization of 125I[Tyr14]orphanin FQ/nociceptin and 125I[Tyr10]orphanin FQ/nociceptin(1–11) binding sites in rat brain

✍ Scribed by Sharon R. Letchworth; John P. Mathis; Grace C. Rossi; Richard J. Bodnar; Gavril W. Pasternak

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 535 KB
• Volume: 423
• Category: Article
• ISSN: 0021-9967
• DOI: 10.1002/1096-9861(20000724)423:2<319::aid-cne9>3.0.co;2-c

✦ Synopsis

The endogenous ligand for the orphan opioid receptor, orphanin FQ/nociceptin (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 peptide. This peptide has been reported in the brain and it has a unique pharmacology. In the present study, we compared the autoradiographic distribution of 125 I[Tyr 14 ]OFQ and 125 I[Tyr 10 ]OFQ(1-11) in coronal rat brain sections. Nonspecific binding was defined with unlabeled OFQ or OFQ(1-11), respectively. Both radioligands demonstrated high levels of specific binding (Ͼ95% of total binding), with no appreciable binding in white matter areas with either ligand. 125 I[Tyr 14 ]OFQ binding was widely distributed throughout the rat brain. In contrast, 125 I[Tyr 10 ]OFQ(1-11) binding was more restricted. The highest 125 I[Tyr 14 ]OFQ binding levels measured in this study were found in the locus coeruleus, an area which contained very low 125 I[Tyr 10 ]OFQ(1-11) binding. Both ligands labeled the cortex, hippocampus and amygdala. In the thalamus, 125 I[Tyr 14 ]OFQ binding was prominent in most nuclei, whereas 125 I[Tyr 10 ]OFQ(1-11) binding was restricted to the midline thalamus. 125 I[Tyr 14 ]OFQ binding was heavy in the suprachiasmatic hypothalamus, and moderate in other hypothalamic nuclei. 125 I[Tyr 10 ]OFQ(1-11) binding in the hypothalamus, however, was present mainly in the ventromedial hypothalamic nucleus. Lower binding levels of both ligands were found 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.