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A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites
Published on: March 1, 2018
La fosforilación y el secuestro de los transportadores de serotonina modulados diferencialmente por los
1Department of Pharmacology and Center for Molecular Neuroscience, School of Medicine, Vanderbilt University, Nashville, TN 37232-6420, USA.
Science (New York, N.Y.)
|July 31, 1999
Resumen
Las drogas psicotrópicas afectan a los transportadores de neurotransmisores como SERT. La unión de ligandos influye en la actividad del transportador, afectando la eficacia del fármaco y los efectos secundarios a través de vías dependientes de PKC.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Farmacología Farmacología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los medicamentos psicotrópicos modulan los sistemas de neurotransmisores.
- Las vías de la quinasa, incluida la proteína quinasa C (PKC), regulan la función del transportador.
- La fosforilación y el secuestro del transportador son mecanismos reguladores clave.
Objetivo del estudio:
- Investigar cómo la ocupación de ligandos afecta la regulación dependiente de la proteína quinasa C (PKC) del transportador de serotonina (SERT).
- Para aclarar el impacto de los ligandos transportados y no transportados en la fosforilación y el secuestro de SERT.
- Comprender la modulación dependiente de la actividad de la recaptación de neurotransmisores.
Principales métodos:
- Estudió los efectos de varios ligandos (serotonina, anfetaminas, cocaína, antidepresivos) en la fosforilación y el secuestro de las SERT.
- Utilizó ensayos bioquímicos para medir la actividad del transportador y los eventos regulatorios.
- Investigó el papel de la PKC en la mediación de estos efectos inducidos por ligandos.
Principales resultados:
- La ocupación de ligandos tuvo un impacto significativo en la fosforilación y el secuestro de SERT.
- Los ligandos transportados (serotonina, anfetaminas) inhibieron la fosforilación SERT dependiente de PKC.
- Los antagonistas no transportados (cocaína, antidepresivos) permitieron la fosforilación SERT pero bloquearon los efectos de la serotonina.
- La serotonina también inhibió el secuestro SERT dependiente de PKC.
Conclusiones:
- La función del transportador de neurotransmisores está modulada por la unión de ligandos de una manera dependiente de la actividad.
- Las acciones de las drogas, incluidas las de las anfetaminas, la cocaína y los antidepresivos, tienen consecuencias no reconocidas previamente en la regulación del transportador.
- Los hallazgos proporcionan información sobre los mecanismos moleculares subyacentes a la eficacia de los fármacos psicotrópicos y sus efectos secundarios.
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