Volatile anaesthetics are known to affect cholinergic receptors. Perturbation of cholinergic signalling can cause cognitive deficits. In this study, we wanted to evaluate acetylcholine‐induced
intracellular signalling following sevoflurane exposure. Methods
Pheochromocytoma12 PC12 cells were exposed to 4.6% sevoflurane for 2 h. Subsequently,
Western blotting was used to measure acetylcholine‐induced phosphorylation of extracellular signal‐regulated kinase 1/2 (ERK) 1/2 and basal Protein kinase B (AKT) phosphorylation.
After exposure, acetylcholine‐induced ERK 1/2 phosphorylation was reduced to 58 ± 8% [95% confidence interval (CI): 38–77%, P = 0.003]
compared with non‐exposed controls. At 30 min after the end of sevoflurane administration [at 0.7% sevoflurane (0.102 mM)], ERK 1/2 phosphorylation remained reduced to 57 ± 7% (95% CI:
39–74%, P = 0.001) and was at 120 min [0.02% (0.003 mM] still reduced to 63 ± 10% (95% CI: 37–88%, P = 0.01), compared
with control. At 360 min after exposure, acetylcholine‐induced ERK 1/2 phosphorylation had recovered to 98 ± 16% (95% CI: 45–152%, P = 0.98) compared with control. In
contrast, immediately after sevoflurane exposure, basal AKT phosphorylation was increased by 228 ± 37% (95% CI: 133–324%, P = 0.02) but had returned to control levels at 30 min
after exposure, 172 ± 67% (95% CI: 0–356%, P = 0.34). Conclusion
Sevoflurane exposure has differential
effects on different intracellular signalling pathways. On one hand, we observed a prolonged attenuation of acetylcholine‐induced ERK 1/2 phosphorylation that persisted even when sevoflurane concentrations close to detection level. On the other hand, basal AKT
phosphorylation was increased twofold during sevoflurane exposure, with a rapid return to baseline levels after exposure. We speculate that the effects on acetylcholine‐induced intracellular signalling observed in our in vitro model could be of relevance also for cholinergic signalling
in vivo following sevoflurane exposure.
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