Inhibition of the MAPK/ERK cascade: a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol.
- Author:
Eugene E FIBUCH
1
;
John Q WANG
Author Information
1. Department of Anesthesiology, University of Missouri-Kansas City School of Medicine, Saint Lukeos Hospital, Kansas City, Missouri 64108, USA.
- Publication Type:Journal Article
- MeSH:
Amnesia;
chemically induced;
enzymology;
Anesthetics, Intravenous;
pharmacology;
Animals;
Cells, Cultured;
Extracellular Signal-Regulated MAP Kinases;
drug effects;
metabolism;
Hippocampus;
cytology;
drug effects;
enzymology;
Long-Term Potentiation;
drug effects;
physiology;
Memory;
drug effects;
physiology;
Mitogen-Activated Protein Kinase 1;
drug effects;
Mitogen-Activated Protein Kinase 3;
drug effects;
Neurons;
drug effects;
enzymology;
Propofol;
pharmacology;
Rats;
Receptors, N-Methyl-D-Aspartate;
metabolism;
Signal Transduction;
drug effects;
physiology;
Transcriptional Activation;
drug effects
- From:
Neuroscience Bulletin
2007;23(2):119-124
- CountryChina
- Language:English
-
Abstract:
Intravenous anesthetics are known to cause amnesia, but the underlying molecular mechanisms remain elusive. To identify a possible molecular mechanism, we recently turned our attention to a key intracellular signaling pathway organized by a family of mitogen-activated protein kinases (MAPKs). As a prominent synapse-to-nucleus superhighway, MAPKs couple surface glutamate receptors to nuclear transcriptional events essential for the development and/or maintenance of different forms of synaptic plasticity (long-term potentiation and long-term depression) and memory formation. To define the role of MAPK-dependent transcription in the amnesic property of anesthetics, we conducted a series of studies to examine the effect of a prototype intravenous anesthetic propofol on the MAPK response to N-methyl-D-aspartate receptor (NMDAR) stimulation in hippocampal neurons. Our results suggest that propofol possesses the ability to inhibit NMDAR-mediated activation of a classic subclass of MAPKs, extracellular signal-regulated protein kinase 1/2 (ERK1/2). Concurrent inhibition of transcriptional activity also occurs as a result of inhibited responses of ERK1/2 to NMDA. These findings provide first evidence for an inhibitory modulation of the NMDAR-MAPK pathway by an intravenous anesthetic and introduce a new avenue to elucidate a transcription-dependent mechanism processing the amnesic effect of anesthetics.
