The orphanin FQ/nociceptin gene: structure, tissue distribution of expression and functional implications obtained from knockout mice

Like other neuropeptides, orphanin FQ/nociceptin (OFQ/N) is encoded by a la rger precursor protein. The cDNA for the OFQ/N precursor has been cloned fr om human, rat, mouse and bovine tissue demonstrating that this peptidergic system serves important functions that have been conserved during evolution . The structural organization of the precursor protein is similar to opioid peptide precursors, supporting the view of a common origin for the opioid systems and the OFQ/N system. In addition to OFQ/N, the precursor may encod e two other biologically active peptides. Anatomic studies have revealed hi gh levels of expression of the OFQ/N messenger RNA in brain structures invo lved in sensory, emotional and cognitive processing. In particular, high le vels of OFQ/N mRNA were detected in thr limbic system, underlining the stre ss attenuating activities that have been described as an important function of OFQ/N. Recently, mutant mice have been generated that lack: the precurs or protein of OFQ/N to further define the physiological functions of the OF Q/N system. The OFQ/N-deficient mice are characterized by an increased sens itivity to stressful stimuli and a lack of habituation to chronic and repea ted stress. This review will summarize recent findings on the molecular bio logy of the OFQ/N precursor and relate it to possible physiological functio ns of this newly discovered neuropeptide system. (C) 2000 Elsevier Science Tnc. All rights reserved.