Mucio-Ramírez S, Miller-Pérez C, Sánchez-Islas E, León-Olea M

Language: Spanish
References: 227
Page: 43-54
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ABSTRACT

Clonation of opioid receptors δ, μ and κ 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 μ, δ and κ, endogenous opioid ligands like ß-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 this 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 de aminoácidos de la N/OFQ. El gen de la PPNOC está conservado en cinco especies animales estudiadas (rata, ratón, porcino, bovino y humano) y se expresa predominantemente en hipotálamo, mesencéfalo, núcleos del lemnisco lateral, oliva superior, núcleo trigeminal espinal y médula espinal. Debido al reciente descubrimiento de este péptido y su receptor, además de su amplia distribución en el sistema nervioso, resulta obvio que su participación en la fisiología y sus probables implicaciones farmacológicas todavía no están completas. La presencia de la N/OFQ en especies de los primeros niveles de la escala filogenética como son los moluscos Helix aspersa, H. pomatia y Cepaea nemoralis, donde se demostró también que la administración de N/OFQ tiene un efecto pronociceptivo similar a la hiperalgesia de los mamíferos, sugieren que este nuevo sistema opioide tiene un origen filogenético temprano y una continuidad funcional durante el curso de la evolución. En este artículo se hace una revisión de la literatura acerca de este nuevo receptor: el ORL-1 y su péptido endógeno, la nociceptina/orfanina FQ.

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