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A tyrosine kinase regulates propofol-induced modulation of the β-subunit of the GABAA receptor and release of intracellular calcium in cortical rat neurones

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Abstract:

Abstract

Propofol, an intravenous anaesthetic, has been shown to interact with the β-subunit of the γ-amino butyric acidA (GABAA) receptor and also to cause changes in [Ca2+]i. The GABAA receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre-incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+]i were investigated. Propofol (3 μg mL−1, 16.8 μM) increased intracellular calcium levels by 122 ± 34% (mean ± SEM) when applied to neurones in calcium free medium. This rise in [Ca2+]i was lowered by 68% when the cells were pre-incubated with the tyrosine kinase inhibitor herbimycin A before exposure to propofol (P < 0.05). Propofol caused an increase (33 ± 10%) in tyrosine phosphorylation, with maximum at 120 s, of the β-subunit of the GABAA-receptor. This tyrosine phosphorylation was decreased after pre-treatment with herbimycin A (44 ± 7%, P < 0.05), and was not affected by the absence of exogenous calcium in the medium. Tyrosine kinase participates in the propofol signalling system by inducing the release of calcium from intracellular stores and by modulating the β-subunit of the GABAA-receptor.

Keywords: 2; 6-di-isopropylphenol; anaesthetic mechanisms; intravenous; neurone; propofol; rat; tyrosine kinase

Document Type: Research Article

DOI: http://dx.doi.org/10.1046/j.1365-201X.2002.00991.x

Affiliations: 1: Division of Experimental Pathology, Lund University, S-205 02 Malmo¨, Sweden. 2: Department of Cell Biology, Faculty of Health Sciences, Linko¨ping University, Linko¨ping, Sweden

Publication date: July 1, 2002

bsc/aps/2002/00000175/00000003/art00007
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