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2001, Número 6

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Salud Mental 2001; 24 (6)


El receptor ORL-1 y su péptido endógeno, la nociceptina/orfanina FQ. Nuevos miembros de la familia de los opioides

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

Idioma: Español
Referencias bibliográficas: 227
Paginas: 43-54
Archivo PDF: 436.23 Kb.


RESUMEN

A la clonación de los receptores opioides δ , μ y κ siguió la identificación y secuenciación de otro miembro de la familia opioide, el receptor ORL-1 (por sus siglas en ingles, opioid receptor like-1). No obstante, su gran homología con los receptores μ, δ y κ , los ligandos opioides endógenos, como la ßendorfina, la dinorfina A y las encefalinas, no presentan gran afinidad por este receptor. Después del descubrimiento del ORL- 1, se aisló su péptido endógeno; éste tiene gran afinidad (nanomolar) para su receptor. Dos grupos de investigación independientes reportaron con este péptido: el grupo de Meunier lo llamó nociceptina y el grupo de Reinscheid, orfanina FQ. El ORL-1 y la nociceptina/orfanina FQ (N/OFQ) tienen una distribución anatómica amplia en el sistema nervioso, principalmente en los núcleos olfatorios, corteza cerebral, hipocampo, región septal, ganglios basales, tálamo, hipotálamo, puente, bulbo, pedúnculos cerebrales, médula espinal y retina, lo que evidencia su participación en diversas funciones cerebrales. La administración de la N/OFQ puede producir hiperalgesia, alodinia, efectos antiopioides o analgesia. Estos efectos dependen básicamente de la dosis y de la vía de administración. Además, alteraciones en la locomoción, en el comportamiento exploratorio motivacional, en la ansiedad, memoria, alimentación y modulación neuroendocrina. La N/OFQ se deriva de un precursor de alto peso molecular, la prepronociceptina (PPNOC), el cual contiene una sola copia de la secuencia 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 compl etas. 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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