M Haines1, L M Mao, L Yang, A Arora, E E Fibuch, J Q Wang. 1. Department of Anesthesiology, University of Missouri-Kansas City School of Medicine, 2411 Holmes Street, Kansas City, MO 64108, USA.
Abstract
BACKGROUND: The ionotropic glutamate receptor is a potential molecular site in the central nervous system that general anaesthetics may interact with to produce some of their biological actions. Protein phosphorylation has been well documented to occur in the intracellular C-terminal domain of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors, which represents a pivotal mechanism for the post-translational modulation of AMPA receptor functions. In this study, we investigated a possible influence of an i.v. anaesthetic agent propofol on the phosphorylation of AMPA receptor GluR1 subunits in cultured neurons. METHODS: The effect of propofol on phosphorylation of GluR1 subunits at serine 831 and 845 was assayed in cultured rat striatal and cortical neurons by western blot with phospho- and site-specific antibodies. RESULTS: Propofol consistently elevated phosphorylation of GluR1 subunits at the C-terminal serine 845 site in both striatal and cortical neurons. The elevation in phosphorylation was concentration-dependent and started at a low concentration (3 microM). This increase in serine 845 phosphorylation was rapid and sustained during the entire course of propofol exposure. In contrast to serine 845, phosphorylation of GluR1 at serine 831 was not altered by propofol in striatal and cortical neurons. Total GluR1 abundance remained unchanged in response to propofol incubation. CONCLUSIONS: These data indicate that propofol possesses the ability to upregulate AMPA receptor GluR1 subunit phosphorylation at a specific serine 845 site in neurons and provide evidence supporting the AMPA receptor as a molecular target for general anaesthetics.
BACKGROUND: The ionotropic glutamate receptor is a potential molecular site in the central nervous system that general anaesthetics may interact with to produce some of their biological actions. Protein phosphorylation has been well documented to occur in the intracellular C-terminal domain of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors, which represents a pivotal mechanism for the post-translational modulation of AMPA receptor functions. In this study, we investigated a possible influence of an i.v. anaesthetic agent propofol on the phosphorylation of AMPA receptor GluR1 subunits in cultured neurons. METHODS: The effect of propofol on phosphorylation of GluR1 subunits at serine 831 and 845 was assayed in cultured rat striatal and cortical neurons by western blot with phospho- and site-specific antibodies. RESULTS:Propofol consistently elevated phosphorylation of GluR1 subunits at the C-terminal serine 845 site in both striatal and cortical neurons. The elevation in phosphorylation was concentration-dependent and started at a low concentration (3 microM). This increase in serine 845 phosphorylation was rapid and sustained during the entire course of propofol exposure. In contrast to serine 845, phosphorylation of GluR1 at serine 831 was not altered by propofol in striatal and cortical neurons. Total GluR1 abundance remained unchanged in response to propofol incubation. CONCLUSIONS: These data indicate that propofol possesses the ability to upregulate AMPA receptor GluR1 subunit phosphorylation at a specific serine 845 site in neurons and provide evidence supporting the AMPA receptor as a molecular target for general anaesthetics.
Authors: Kwan Young Lee; Yujin Jang; Min Hee Lee; Young Im Kim; Sung-Cherl Jung; Seung-Yun Han; Se Hoon Kim; Hyung Seo Park; Dong Kwan Kim Journal: Clin Psychopharmacol Neurosci Date: 2018-05-31 Impact factor: 2.582