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Una función protectora para los receptores activados por proteasa en las vías respiratorias
1Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia. t.cocks@pharmacology.unimelb.edu.au
Nature
|March 23, 1999
Resumen
La tripsina activa el receptor 2 activado por proteasa (PAR2) en el epitelio de las vías respiratorias, desencadenando la liberación de prostaglandina E2 (PGE2) para la protección de las vías respiratorias. Este mecanismo inhibe la broncoconstricción, destacando una nueva vía protectora en las vías respiratorias.
Área de la Ciencia:
- Medicina Pulmonar La medicina pulmonar es el tratamiento de las enfermedades pulmonares.
- Biología celular Biología celular.
- Gastroenterología y Gastroenterología.
Sus antecedentes:
- El intestino superior utiliza la prostaglandina E2 (PGE2) y los receptores activados por proteasa (PAR) para la protección epitelial contra la tripsina.
- El epitelio de las vías respiratorias comparte similitudes con el epitelio intestinal y expresa PAR2, un receptor clave en este mecanismo de protección.
- El epitelio de las vías respiratorias es una fuente significativa de PGE2, lo que sugiere un papel potencial en la citoprotección de las vías respiratorias.
Objetivo del estudio:
- Para investigar el papel de la PAR2 epitelial bronquial en la citoprotección de las vías respiratorias dependiente de los prostanoides.
- Para determinar si el PAR2 activado con tripsina puede inducir respuestas protectoras en las vías respiratorias.
Principales métodos:
- Inmunohistoquímica para evaluar la co-localización de PAR2 y tripsina en el epitelio de las vías respiratorias.
- Estudios ex vivo en preparaciones aisladas de las vías respiratorias de varias especies (ratón, rata, cobaya, humano) para medir las respuestas a la activación de PAR2.
- Estudios in vivo en ratas anestesiadas para evaluar el efecto de la activación de PAR2 en la broncoconstricción.
- Experimentos que involucran la desensibilización PAR2 para evaluar los mecanismos de recuperación.
Principales resultados:
- La activación de PAR2 en el epitelio de las vías respiratorias desencadena la liberación de productos de ciclooxigenasa, lo que lleva a la relajación de las vías respiratorias.
- La activación de PAR2 inhibe significativamente la broncoconstricción en las vías respiratorias aisladas e in vivo.
- Después de la desensibilización PAR2, la respuesta a la tripsina se recupera rápidamente a través de la síntesis y el tráfico de proteínas de novo.
Conclusiones:
- La activación del PAR2 epitelial inicia una respuesta broncoprotectora potente y dependiente de los prostanoides.
- La tripsina liberada desde el epitelio puede activar PAR2, lo que lleva a la protección de las vías respiratorias y la inhibición de la broncoconstricción.
- Esta vía representa un mecanismo fisiológico significativo para la citoprotección de las vías respiratorias.
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