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Orexin a phosphorylates the γ‐Aminobutyric acid type A receptor β 2 subunit on a serine residue and changes the surface expression of the receptor in SH‐SY5Y cells exposed to propofol
Author(s) -
Andersson Henrik,
Björnström Karin,
Eintrei Christina,
Sundqvist Tommy
Publication year - 2015
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23631
Subject(s) - gabaa receptor , sh sy5y , orexin a , gabaa rho receptor , phosphorylation , orexin , receptor , serine , chemistry , microbiology and biotechnology , protein subunit , biophysics , biology , biochemistry , neuropeptide , cell culture , gene , neuroblastoma , genetics
Propofol activates the γ‐aminobutyric acid type A receptor (GABA A R) and causes a reversible neurite retraction, leaving a thin, thread‐like structure behind; it also reverses the transport of vesicles in rat cortical neurons. The awakening peptide orexin A (OA) inhibits this retraction via phospholipase D (PLD) and protein kinase Cɛ (PKCɛ). The human SH‐SY5Y cells express both GABA A Rs and orexin 1 and 2 receptors. These cells are used to examine the interaction between OA and the GABA A R. The effects of OA are studied with flow cytometry and immunoblotting. This study shows that OA stimulates phosphorylation on the serine residues of the GABA A R β 2 subunit and that the phosphorylation is caused by the activation of PLD and PKCɛ. OA administration followed by propofol reduces the cell surface expression of the GABA A R, whereas propofol stimulation before OA increases the surface expression. The GABA A R β 2 subunit is important for receptor recirculation, and the effect of OA on propofol‐stimulated cells may be due to a disturbed recirculation of the GABA A R. © 2015 Wiley Periodicals, Inc.