Orexin a phosphorylates the γ-Aminobutyric acid type A receptor β2 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 (GABAA 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 GABAA Rs and orexin 1 and 2 receptors. These cells are used to examine the interaction between OA and the GABAA 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 GABAA R β2 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 GABAA R, whereas propofol stimulation before OA increases the surface expression. The GABAA R β2 subunit is important for receptor recirculation, and the effect of OA on propofol-stimulated cells may be due to a disturbed recirculation of the GABAA R.
Department of Anaesthesiology and Intensive Care, Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Henrik
H
Andersson
Department of Anaesthesiology and Intensive Care, Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Karin
K
Björnström
Department of Anaesthesiology and Intensive Care, Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Christina
C
Eintrei
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Tommy
T
Sundqvist
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism*; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D018686:Anesthetics, Intravenous; D000068797:Orexins; D011963:Receptors, GABA-A; D012694:Serine; D015742:Propofol
AB_10675844; AB_10712311; AB_1269637; AB_1566589; AB_2247467; AB_307184; AB_307187; GABAAR; cell signaling; orexin; propofol