The opioid receptor like-1 and its endogenous peptide nociceptin/orphanin FQ.: New members of the opioid family

Clonation of opioid receptors delta, mu and kappa was followed by identification and sequencing of and other member of the opioid family: the opioid receptor like-1 (ORL-1). Although they share similarities with receptors mu, delta and kappa, endogenous opioid ligands like beta-endorphin, dynorphin A and enkephalins do not have great affinity for this receptor. After the discovery of ORL-1, its endogenous peptide was isolated. This peptide present a nanomolar affinity with its receptor. Two different research groups reported this peptide: Meunier et al. (1995) called it nociceptin, and Reinscheid et al. (1995) called it orphanin FQ. ORL-1 and nociceptin/orphanin FQ (N/OFQ) have a wide anatomical distribution in the nervous system, mainly in the olfactory nucleus, cerebral cortex, hippocampus, septal region, basal ganglia, thalamus, hypothalamus, pons, medulla, cerebral peduncle, spinal cord and retina. This anatomical distribution evidences its role in different cerebral functions. Administration of N/OFQ may have hyperalgesic, allodinic, antiopioid or even analgesic effects. Basically, the effects are both related with dose and administration route. Besides, it may produce many behavioral effects which especially modify locomotion, exploratory behavior, motivation, anxiety, memory, food intake and neuroendocrine modulation. N/OFQ is derived from a protein precursor of high molecular weight called prepronociceptin (PPNOC), which contains only one copy of the aminoacid sequence of N/OFQ. The gene of PPNOC is conserved in five mammals (rat, mouse, porcine, bovine and human species). PPNOC is predominantly expressed in hypothalamus, midbrain, lateral lemniscus, superior olive, trigeminal spinal nucleus of the brainstem and spinal cord. Given the recent discovery of dais peptide and its receptor, and the fact that it has a wide localization within the CNS, it is obvious that the study of its physiology and pharmacology is not totally finished. Two evidences -the presence of N/OFQ in species that belong to low levels of phylogenetic scale like mollusk Helix-aspersa, H. pomatia y Cepaea nemoralis and the pronociceptive effect, similar to the hyperalgesia in mammals-support the idea that this new opioid system has an early phylogenetic origin and a functional continuity during the course of evolution. In this paper we review the literature concerning this new receptor/peptide opioid system ORL-1 and its endogenous peptide nociceptin/orphanin FQ.