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

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.