Orexin A Phosphorylates the gamma-Aminobutyric Acid Type A Receptor beta(2) Subunit on a Serine Residue and Changes the Surface Expression of the Receptor in SH-SY5Y Cells Exposed to Propofol
2015 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 93, no 11, 1748-1755 p.Article in journal (Refereed) Published
Propofol activates the gamma-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 CE (PKCE). 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 GABAAR. 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 beta(2) subunit and that the phosphorylation is caused by the activation of PLD and PKCE. 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 beta(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. (C) 2015 Wiley Periodicals, Inc.
Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2015. Vol. 93, no 11, 1748-1755 p.
orexin; propofol; GABAAR; cell signaling; AB_10675844; AB_1269637; AB_10712311; AB_2247467; AB_307187; AB_307184; AB_1566589
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-122517DOI: 10.1002/jnr.23631ISI: 000362831800013PubMedID: 26283475OAI: oai:DiVA.org:liu-122517DiVA: diva2:868052
Funding Agencies|County Council of Ostergotland ALF Grants; Linkoping University Hospital; Ella and Henry Stahl Research Foundation2015-11-092015-11-062016-04-12