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2004, Número 2

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Salud Mental 2004; 27 (2)


El polipéptido activador de la adenilato ciclasa de la pituitaria (PACAP): actualización de conocimientos

Mucio-Ramírez S, Miller-Pérez C, Curras-Collazo M, León-Olea M

Idioma: Español
Referencias bibliográficas: 154
Paginas: 55-69
Archivo PDF: 297.04 Kb.


RESUMEN

Después del descubrimiento de los factores hipotalámicos hipofisiotróficos, como el factor liberador de la hormona luteinizante, de la tirotrófica, de la hormona del crecimiento y de la corticotrofina, se caracterizaron los factores liberadores de la hormona folículo estimulante y de la hormona prolactina. Sin embargo, algunos estudios mostraron que había células no descritas, que supuestamente requerían un factor hipotalámico. Lo anterior llevó a pensar en la existencia de un nuevo factor hipofisiotrófico, lo que a su vez condujo al descubrimiento del polipéptido activador de la adenilato ciclasa de la pituitaria (PACAP) por Miyata y colaboradores en 1998. Su nombre proviene del efecto que ejerce sobre las células de la pituitaria, ya que incrementa los niveles de AMP cíclico (AMPc) y causa la liberación de diferentes hormonas hipofisiarias. Como este péptido tiene una amplia distribución anatómica y participa en diversas funciones cerebrales, se despertó el interés de varios grupos de investigación por estudiar los efectos farmacológicos y las funciones biológicas en las que el PACAP participa. En esta revisión se presenta la información más reciente de las múltiples acciones fisiológicas que tiene el PACAP y sus receptores en el Sistema Nervioso Central (SNC) y en otros sistemas.
El PACAP es un péptido de 38 aminoácidos, aislado de extractos de hipotálamo de oveja. El PACAP es miembro de la superfamilia secretina/hormona de crecimiento/glucagon/péptido intestinal vaso activo, y su secuencia es la más conservada filogenéticamente. Existen dos formas biológicamente activas del PACAP: una de 38 aminoácidos y otra truncada de 27; los dos péptidos están amidados en su extremo carboxilo terminal. El PACAP comparte una gran homología estructural con todos los péptidos pertenecientes a esta familia, principalmente con el péptido intestinal vasoactivo (VIP) de porcino, con el que muestra 68% de homología en su porción aminoterminal 1-28. La clonación molecular del ADN complementario (cDNA) del precursor del PACAP-38 de rata, ratón, bovino y humano, mostró que la secuencia de aminoácidos es 100% idéntica entre ellos. La secuencia del PACAP se identificó en diferentes especies de vertebrados y de algunos invertebrados, como los tunicados, y en anélidos. El PACAP de estas especies muestra un alto grado de identidad con el PACAP del humano con una diferencia de uno a cuatro aminoácidos. Este patrón de conservación en la secuencia de aminoácidos en las diferentes especies animales muestra la importancia biológica de este neuropéptido. Entre las funciones más relevantes del PACAP están las de ser un factor hipofisiotrófico y un neuromodulador. Los receptores para el PACAP pertenecen a la familia de los receptores acoplados a proteínas Gs que tienen siete asas transmembranales. El PACAP produce sus efectos biológicos al unirse con al menos tres tipos de receptores: los PAC-1, VPAC1 y VPAC2. El receptor PAC-1 tiene más afinidad de unión con el PACAP-38 (Kd=0.5 nM) y el PACAP-27 (Kd=2.0 nM). Los estudios de la distribución anatómica de los mRNA que codifican para el PACAP y sus receptores demuestran que se expresan desde las primeras etapas embrionarias en el ratón. El PACAP se distribuye ampliamente en el Sistema Nervioso Central, en el Sistema Nervioso Periférico y en las gónadas. En el SNC de la rata adulta se encontraron células y fibras inmunorreactivas a PACAP-38 y PACAP-27, distribuidas en la corteza cerebelar, hipocampo, septum, tálamo, núcleos supraóptico y paraventricular del hipotálamo, eminencia media, tallo cerebral y médula espinal. En testículos de rata y ratón se encontró una alta concentración de PACAP. Otros tejidos y órganos con células y fibras positivas a PACAP son las glándulas hipófisis, adrenales, pineal y salivales, así como el tracto gastrointestinal, el páncreas, la retina, y algunos ganglios simpáticos. El PACAP cumple con los criterios para considerarlo un factor hipofisiotrófico, ya que está presente en neuronas hipotalámicas que proyectan al sistema portahipofisiario. Asimismo, en la sangre portahipofisiaria interactúa con receptores específicos localizados en las células de la hipófisis y los regula.


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