Propofol-Induced Anesthesia in Mice Is Mediated by γ-Aminobutyric Acid-A and Excitatory Amino Acid Receptors

Irifune, Masahiro; Takarada, Tohru; Shimizu, Yoshitaka; Endo, Chie; Katayama, Sohtaro; Dohi, Toshihiro; Kawahara, Michio

doi:10.1213/01.ane.0000059742.62646.40

Cited by 83 publications

(46 citation statements)

References 24 publications

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“…By contrast, propofol is considered to be less likely to produce anaesthetic effects through an NMDAR-dependent mechanism. This is because a large number of studies have shown that propofol anaesthetises via enhancing GABA-ergic transmission [18,19]. Therefore, propofol may be a more appropriate anaesthetic for such patients.…”

Section: Discussionmentioning

confidence: 99%

Anaesthesia for a patient with paraneoplastic limbic encephalitis with ovarian teratoma: relationship to anti‐N‐methyl‐d‐aspartate receptor antibodies

Kawano¹,

Hamaguchi

Kawahito

et al. 2011

Anaesthesia

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SummaryParaneoplastic limbic encephalitis associated with ovarian teratoma has recently been related to the development of antibodies to specific heteromers of the N-methyl-D-aspartate receptor and exhibits various manifestations including psychiatric symptoms, hypoventilation, seizures and derangement of autonomic nervous system function. Although recovery can sometimes occur spontaneously, early tumour resection with immunotherapy facilitates earlier recovery. Herein, we describe anaesthetic management of a 20-year-old woman who developed general convulsions and decreased level of consciousness, whom we suspected of having paraneoplastic limbic encephalitis and was scheduled for left ovarian tumour resection. Anaesthetic management was successful with no complications but the case acts as focus of discussion for the potential interaction of N-methyl-D-aspartate receptors and anaesthetic sensitivity.

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Section: Discussionmentioning

confidence: 99%

Anaesthesia for a patient with paraneoplastic limbic encephalitis with ovarian teratoma: relationship to anti‐N‐methyl‐d‐aspartate receptor antibodies

Kawano¹,

Hamaguchi

Kawahito

et al. 2011

Anaesthesia

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“…Immediately after drug injection, each animal was placed in a chamber (20 Â 28 Â 15 cm) with an electric heat pad, and the righting reflex was assessed every 2 minutes for a maximum of 2 hours. Anesthesia was evaluated using the following scoring system (Irifune et al, 2003): 0, normal righting reflex; 1, righting within 2 seconds; 2, righting latency 2-10 seconds; 3, no righting within 10 seconds. Anesthetic scores were determined every 2 minutes as the median of three trials.…”

Section: Methodsmentioning

confidence: 99%

Propofol Anesthesia Is Reduced in Phospholipase C–Related Inactive Protein Type-1 Knockout Mice

Nikaido

Furukawa

Shimoyama

et al. 2017

J Pharmacol Exp Ther

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The GABA type A receptor (GABA A -R) is a major target of intravenous anesthetics. Phospholipase C-related inactive protein type-1 (PRIP-1) is important in GABA A -R phosphorylation and membrane trafficking. In this study, we investigated the role of PRIP-1 in general anesthetic action. The anesthetic effects of propofol, etomidate, and pentobarbital were evaluated in wild-type and PRIP-1 knockout (PRIP-1 KO) mice by measuring the latency and duration of loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR). The effect of pretreatment with okadaic acid (OA), a protein phosphatase 1/2A inhibitor, on propofol-and etomidate-induced LORR was also examined. PRIP-1 deficiency provided the reduction of LORR and LTWR induced by propofol but not by etomidate or pentobarbital, indicating that PRIP-1 could determine the potency of the anesthetic action of propofol. Pretreatment with OA recovered the anesthetic potency induced by propofol in PRIP-1 KO mice. OA injection enhanced phosphorylation of cortical the GABA A -R b3 subunit in PRIP-1 KO mice. These results suggest that PRIP-1-mediated GABA A -R b3 subunit phosphorylation might be involved in the general anesthetic action induced by propofol but not by etomidate or pentobarbital.

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“…Presumably because of the improvement in muscle coordination, PRO-treated mice also showed normalization of righting times. Despite the well-known ability of PRO to enhance GABA A R activity (Belelli et al, 1999;Jurd et al, 2003), causing anesthesia on higher-dose intraperitoneal injection (e.g., 140 mg/ kg; Irifune et al, 2003), the low doses of PRO used in this study did not appear to have anesthetic or sedative effects. Because a large reduction for GABA A R-mediated inhibitory transmission was also found in the tg271Q-300 mice (Becker et al, 2002) and mice carrying a point mutation in the ␤ 3 subunit of the GABA A R display a reduction in the loss of the righting reflex after PRO treatment (Jurd et al, 2003), a pleiotropic effect of subanesthetic PRO concentrations at both GABA A Rs and GlyRs cannot be excluded.…”

Section: Discussionmentioning

confidence: 65%

Propofol Restores the Function of “Hyperekplexic” Mutant Glycine Receptors inXenopusOocytes and Mice

O'Shea¹,

Becker²,

Weiher³

et al. 2004

J. Neurosci.

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Human hereditary hyperekplexia ("startle disease") is a neurological disorder characterized by exaggerated, convulsive movements in response to unexpected stimuli. Molecular genetic studies have shown that this disease is often caused by amino acid substitutions at arginine 271 to glutamine or leucine of the ␣ 1 subunit of the inhibitory glycine receptor (GlyR). When exogenously expressed in Xenopus oocytes, agonist responses of mutant ␣ 1 (R271Q) and ␣ 1 (R271L) GlyRs show higher EC 50 values and lower maximal inducible responses (relative efficacies) compared with oocytes expressing wild-type ␣ 1 GlyR subunits. Here, we report that the maximal glycine-induced currents (I max ) of mutant ␣ 1 (R271Q) and ␣ 1 (R271L) GlyRs were dramatically potentiated in the presence of the anesthetic propofol (PRO), whereas the I max of wild-type ␣ 1 receptors was not affected. Quantitative analysis of the agonist responses of the isofunctionally substituted ␣ 1 (R271K) mutant GlyR revealed that saturating concentrations of PRO decreased the EC 50 values of both glycine and the partial agonist ␤-alanine by Ͼ10-fold, with relative efficacies increasing by 4-and 16-fold, respectively. Transgenic (tg) mice carrying the ␣ 1 (R271Q) mutation (tg271Q-300) have both spontaneous and induced tremor episodes that closely resemble the movements of startled hyperekplexic patients. After treatment with subanesthetic doses of PRO, the tg271Q-300 mutant mice showed temporary reflexive and locomotor improvements that made them indistinguishable from wild-type mice. Together, these results demonstrate that the functional and behavioral effects of hyperekplexia mutations can be effectively reversed by drugs that potentiate GlyR responses.

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Propofol-Induced Anesthesia in Mice Is Mediated by γ-Aminobutyric Acid-A and Excitatory Amino Acid Receptors

Abstract: We examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol-induced anesthesia in mice. The results suggest that propofol anesthesia is mediated, at least in part, by both GABA(A) and excitatory amino acid receptors.

Cited by 83 publications

References 24 publications

Anaesthesia for a patient with paraneoplastic limbic encephalitis with ovarian teratoma: relationship to anti‐N‐methyl‐d‐aspartate receptor antibodies

Anaesthesia for a patient with paraneoplastic limbic encephalitis with ovarian teratoma: relationship to anti‐N‐methyl‐d‐aspartate receptor antibodies

Propofol Anesthesia Is Reduced in Phospholipase C–Related Inactive Protein Type-1 Knockout Mice

Propofol Restores the Function of “Hyperekplexic” Mutant Glycine Receptors inXenopusOocytes and Mice

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