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Asignación de subtipos de proteínas G a receptores específicos que inducen la inhibición de las corrientes de calcio
C Kleuss1, J Hescheler, C Ewel
1Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Germany.
Nature
|September 5, 1991
Resumen
Los investigadores identificaron subtipos específicos de proteínas G (Go1 y Go2) responsables de inhibir los canales de calcio en las células secretoras. Este hallazgo aclara cómo los receptores muscarínicos y somatostatina regulan las respuestas celulares.
Área de la Ciencia:
- Biología celular Biología celular.
- Neurofarmacología y Neurofarmacología.
- Fisiología Molecular Fisiología Molecular
Sus antecedentes:
- Los receptores de membrana plasmática inhiben los canales de Ca2+ dependientes del voltaje en las células secretoras.
- Esta inhibición está mediada por las proteínas G sensibles a las toxinas de la tos ferina.
- Existen diferentes subunidades alfa de la proteína G, pero sus funciones específicas en la inhibición mediada por receptores no están claras.
Objetivo del estudio:
- Para determinar qué subtipos específicos de proteínas G median la inhibición del canal Ca2+ por receptores distintos de la membrana plasmática.
- Aclarar los mecanismos moleculares subyacentes a la señalización del calcio regulado por los receptores en las células pituitarias.
Principales métodos:
- Inyección intranuclear de oligonucleótidos antisense en las células GH3 de la hipófisis de rata.
- Utilizó tecnología antisentido para atacar e inhibir selectivamente subtipos específicos de proteínas G.
- Se midió el impacto funcional en la actividad del canal Ca2+ dependiente de la tensión.
Principales resultados:
- Estableció el papel esencial de las proteínas G de tipo Go en la inhibición del canal Ca2+.
- Se demostró que el subtipo Go1 media la inhibición a través de los receptores muscarínicos.
- Se demostró que el subtipo Go2 media la inhibición a través de los receptores de somatostatina.
Conclusiones:
- Los subtipos Go1 y Go2 de las proteínas G de tipo Go median diferencialmente la inhibición del canal Ca2+ por los receptores muscarínicos y somatostatina, respectivamente.
- Proporciona una comprensión molecular detallada de las vías de señalización de los receptores acoplados a proteínas G.
- Avanza el conocimiento en la regulación de la homeostasis del calcio en las células secretoras.
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