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

Pharmacology
|September 14, 2011
PubMed

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.

Related Concept Videos

Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
Opioid Analgesics: Morphine and Other Natural Cogeners01:20

Opioid Analgesics: Morphine and Other Natural Cogeners

Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...