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La somatostatina estimula los canales K+ activados por Ca(2+) a través de la desfosforilación de proteínas
R E White1, A Schonbrunn, D L Armstrong
1Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Nature
|June 13, 1991
Resumen
La somatostatina, un neuropéptido, activa los canales de potasio de gran conductividad (BK) en las células tumorales de la hipófisis. Esta activación se produce a través de la desfosforilación de proteínas, no los iones directos o los efectos de la proteína G.
Área de la Ciencia:
- La neuroendocrinología en neuroendocrinología.
- Fisiología celular Fisiología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La somatostatina es un neuropéptido que regula la secreción en varios tejidos.
- En las células tumorales de la pituitaria, la somatostatina inhibe la secreción a través de dos vías sensibles a la toxina de la tos ferina.
- Una vía inhibe la adenilil ciclasa; la otra es un mecanismo independiente de la cAMP que afecta el influjo de Ca2+.
Objetivo del estudio:
- Aclarar el mecanismo electrofisiológico predominante de la acción de la somatostatina en las células tumorales de la pituitaria.
- Para identificar los canales iónicos específicos y las vías de señalización involucradas en los efectos inhibidores de la somatostatina.
Principales métodos:
- Registros electrofisiológicos de células tumorales de la hipófisis de mamíferos metabólicamente intactas.
- Investigación de los efectos de la somatostatina en la actividad de los canales iónicos.
- Análisis de las funciones de las proteínas Ca2+, cAMP y G en la señalización de la somatostatina.
Principales resultados:
- La somatostatina aumenta significativamente la actividad de los canales K+ de gran conductividad Ca2+ y activados por voltaje (BK).
- Esta activación del canal BK inducida por la somatostatina es independiente de los efectos directos de las proteínas Ca2+, cAMP o G.
- El mecanismo primario involucra a la somatostatina estimulando la actividad del canal BK a través de la desfosforilación de proteínas.
Conclusiones:
- El principal efecto electrofisiológico de la somatostatina en las células tumorales de la hipófisis es la estimulación de los canales BK.
- La desfosforilación de proteínas se identifica como el evento clave de señalización que media la acción de la somatostatina en los canales BK.
- Este hallazgo aclara un mecanismo previamente no identificado de somatostatina independiente de la cAMP.
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