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Sevoflurane inhibits the µ-opioid receptor function expressed in Xenopus oocytes
Kouichiro Minami1, Yuka Sudo, Toru Yokoyama
1Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Tochigi, Japan. kminami@med.uoeh-u.ac.jp
Abstract:
Sevoflurane is widely used for anesthesia, and is commonly used together with opioids in clinical practice. However, the effects of sevoflurane on μ-opioid receptor (μOR) functions is still unclear. In this study, the effects of sevoflurane on μOR functions were analyzed by using Xenopus oocytes expressing a μOR fused to chimeric Gα protein G(qi5) (μOR-G(qi5)). Sevoflurane by itself did not elicit any currents in oocytes expressing μOR-G(qi5), whereas sevoflurane inhibited the [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO)-induced Cl(-) currents at clinically used concentrations. Sevoflurane did not affect the Cl(-) currents induced by AlF(4)(-), which directly led to activation of G proteins. The inhibitory effects of sevoflurane on the DAMGO-induced currents were not observed in oocytes pretreated with the protein kinase C (PKC) inhibitor GF109203X. These findings suggest that sevoflurane would inhibit μOR function. Further, the mechanism of inhibition by sevoflurane would be mediated by PKC.
Insights
Sevoflurane, an anesthetic, inhibits μ-opioid receptor (μOR) function. This effect is mediated by protein kinase C (PKC) and occurs at clinically relevant concentrations.
Area of Science:
- Anesthesiology
- Neuroscience
- Pharmacology
Background:
- Sevoflurane is a common anesthetic agent.
- Opioids are frequently co-administered with sevoflurane.
- The precise impact of sevoflurane on μ-opioid receptor (μOR) activity remains incompletely understood.
Purpose of the Study:
- To investigate the effects of sevoflurane on μOR signaling pathways.
- To elucidate the underlying mechanisms of sevoflurane's interaction with μOR.
Main Methods:
- Utilized Xenopus oocytes expressing μOR fused to a chimeric Gα protein (μOR-G(qi5)).
- Assessed sevoflurane's impact on agonist-induced currents and direct G protein activation.
- Examined the role of protein kinase C (PKC) in sevoflurane's modulatory effects.
Main Results:
- Sevoflurane alone did not activate μOR-G(qi5) expressing oocytes.
- Clinically relevant sevoflurane concentrations inhibited DAMGO-induced currents.
- Sevoflurane's inhibition was PKC-dependent and did not affect direct G protein activation.
Conclusions:
- Sevoflurane inhibits μOR function.
- The inhibitory mechanism involves protein kinase C (PKC) activation.
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