Strychnine-Sensitive Glycine Receptors Mediate the Analgesic but Not the Hypnotic Effects of Emulsified Volatile Anaesthetics

Ahrens, Jörg; Leuwer, Martin; Haeseler, Gertrud

doi:10.1159/000112943

Cited by 3 publications

(4 citation statements)

References 13 publications

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“…propofol and volatile anaesthetics) activate or co-activate glycine receptors. This glycine modulatory mechanism has been linked to the anti-nociceptive effect of anaesthetics [22,23] . The discrepancy between the results of Fodor et al [21] and the results of other groups might be explained by the difference in subunit composition between native receptors and heterologously expressed homomeric receptors.…”

Section: Discussionmentioning

confidence: 99%

The Anaesthetic Steroid Alphaxalone Positively Modulates α<sub>1</sub>-Glycine Receptor Function

Ahrens¹,

Leuwer

Demir³

et al. 2008

Pharmacology

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Inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the processing of nociceptive signals, and mainly involves glycine. We have studied the effects of alphaxalone on α₁ homomeric glycine receptors expressed in a mammalian expression system (HEK 293 cells) using the whole-cell patch-clamp technique. Our experiments showed a coactivating effect of alphaxalone with a concentration for half-maximum activation (EC₅₀) of the effect of a low glycine concentration (EC₂₀) of 70.9 ± 21.5 µmol/l. Taking into account the results of other groups, our study suggests that neuroactive steroids might be an interesting class of compounds to probe subunit-specific effects of glycine receptors.

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Section: Discussionmentioning

confidence: 99%

The Anaesthetic Steroid Alphaxalone Positively Modulates α<sub>1</sub>-Glycine Receptor Function

Ahrens¹,

Leuwer

Demir³

et al. 2008

Pharmacology

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“…The action of propofol, alphaxalone, pentobarbitone, halothane, and enflurane was studied on α1 GlyRs expressed in Xenopus oocytes. All anesthetics potentiated receptor function, , and GlyR potentiation was shown to be responsible for their analgesic but not their hypnotic effects . Fluorothyl, a convulsant, had no effect on α1 GlyRs expressed in HEK293 cells while its isomer iso-fluorothyl, an anesthetic, potentiated GlyR-mediated currents .…”

Section: Modulators Of the Inhibitory Glycine Receptormentioning

confidence: 95%

“…All anesthetics potentiated receptor function, 118,120 and GlyR potentiation was shown to be responsible for their analgesic but not their hypnotic effects. 121 Fluorothyl, a convulsant, had no effect on α1 GlyRs expressed in HEK293 cells while its isomer iso-fluorothyl, an anesthetic, potentiated GlyR-mediated currents. 122 Pentobarbital at 30 μM prolonged the decay time constant of glycinergic miniature inhibitory postsynaptic currents (mIPSCs) in spinal dorsal horn neurons without affecting their amplitude and frequency.…”

Section: T H Imentioning

confidence: 96%

Modulators of the Inhibitory Glycine Receptor

Breitinger

2020

ACS Chem. Neurosci.

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The inhibitory glycine receptor is a member of the Cys-loop superfamily of ligand-gated ion channels. It is the principal mediator of rapid synaptic inhibition in the spinal cord and brainstem and plays an important role in the modulation of higher brain functions including vision, hearing, and pain signaling. Glycine receptor function is controlled by only a few agonists, while the number of antagonists and positive or biphasic modulators is steadily increasing. These modulators are important for the study of receptor activation and regulation and have found clinical interest as potential analgesics and anticonvulsants. Highresolution structures of the receptor have become available recently, adding to our understanding of structure−function relationships and revealing agonistic, inhibitory, and modulatory sites on the receptor protein. This Review presents an overview of compounds that activate, inhibit, or modulate glycine receptor function in vitro and in vivo.

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“…Spinal α1-β GlyRs regulate muscle tone and movement, and immunocytochemical and electrophysiological evidence reveal GlyR α3β subunits as important mediator of glycinergic inhibitory neurotransmission in nociceptive sensory neuronal circuits in the superficial laminae of the spinal cord dorsal horn (Lynch 2009 ). Even though GABA is the more abundant inhibitory neurotransmitter, the GlyR is a major inhibitory signaling device in control of nociception (Ishikawa et al 2000 ; Yaksh 1989 ) and analgesia (Ahrens et al 2008 ; Breitinger and Breitinger 2016 ; Xiong et al 2011 ). Intrathecal injections of strychnine, a highly selective GlyR antagonist, inhibits spinal GlyRs resulting in profound agitation and hypersensitization of treated animals to tactile stimuli (Raafat et al 2010 ; Yaksh 1989 ).…”

Section: Role Of Inhibitory Transmission In Pain Modulationmentioning

confidence: 99%

Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain

Breitinger

2023

Mol Med

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Pain, although unpleasant, is an essential warning mechanism against injury and damage of the organism. An intricate network of specialised sensors and transmission systems contributes to reception, transmission and central sensitization of pain. Here, we briefly introduce some of the main aspects of pain signal transmission, including nociceptors and nociceptive signals, mechanisms of inflammatory and neuropathic pain, and the situation of diabetes-associated neuropathic pain. The role of glia—astrocytes, microglia, satellite glia cells—and their specific channels, transporters and signaling pathways is described. A focus is on the contribution of inhibitory synaptic signaling to nociception and a possible role of glycine receptors in glucose-mediated analgesia and treatment-induced diabetic neuropathy. Inhibitory receptors such as GABAA- and glycine receptors are important contributors to nociceptive signaling; their contribution to altered pain sensation in diabetes may be of clinical relevance, and they could be promising therapeutic targets towards the development of novel analgesics.

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Strychnine-Sensitive Glycine Receptors Mediate the Analgesic but Not the Hypnotic Effects of Emulsified Volatile Anaesthetics

Cited by 3 publications

References 13 publications

The Anaesthetic Steroid Alphaxalone Positively Modulates α<sub>1</sub>-Glycine Receptor Function

The Anaesthetic Steroid Alphaxalone Positively Modulates α<sub>1</sub>-Glycine Receptor Function

Modulators of the Inhibitory Glycine Receptor

Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain

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