Year-end Sale % OFF 
Abstract
The inhibitory glycine receptor (GlyR) plays an important role in rapid synaptic inhibition in mammalian spinal cord, brainstem, higher brain centers, and is involved in transmission of nociceptive signals. Glucose and related mono- and disaccharides potentiate currents mediated by recombinant α1, α1-β, and α3 GlyRs. Here, we confirmed the specific potentiation of α3 GlyR signaling by glucose through: (i) patch-clamp electrophysiology on recombinant receptors; and (ii) by verifying in vitro data in a mouse model in vivo. Mice were intraperitoneally (IP) injected with glucose (2 g/kg) or vehicle, and then challenged with sublethal doses of strychnine (0.2 mg/kg and 0.5 mg/kg). Pain-related behavior was assessed using two established models: (i) touch sensitivity tests using von Frey filaments; and (ii) hotplate assay. We observed a reduction of pain sensitivity in glucose-treated mice relative to vehicle-treated control mice. Injection of strychnine resulted in an increased sensitivity to tactile and heat stimuli, which was reversed in the presence of glucose. Analgesic effects of glucose were more pronounced in von Frey experiments, consistent with the established use of this model for neuropathic pain. Overall, glucose showed mild analgesic effects and was able to compensate for strychnine-induced allodynia in mice. Since the action of strychnine is specific for GlyR, these experiments show for the first time an in vivo potentiation of GlyR activity by glucose and suggest a molecular mechanism for glucose-mediated analgesia.
Highlights
The inhibitory glycine receptor (GlyR) is one of the principal mediators of rapid synaptic inhibition in the mammalian spinal cord, brainstem, and higher brain centers
Since α3 GlyRs are involved in pain signaling pathways, we investigated the influence of glucose on in vivo pain-related behavior in two different mouse models, namely von Frey filaments and hotplate tests
We concluded that inhibition of α3 GlyRs by strychnine is independent of the absence or presence of glucose (Figure 2D)
Summary
The inhibitory glycine receptor (GlyR) is one of the principal mediators of rapid synaptic inhibition in the mammalian spinal cord, brainstem, and higher brain centers It is a member of the Cys-loop family of ligand-gated ion channel receptors, which includes nicotinic acetylcholine; GABAA and serotonin type 3 (5-HT3) receptors. Specific amino acids enhancing the effects of alcohol and anesthetics were suggested to border a water-filled cavity between transmembrane domains 2–3 (Mihic et al, 1997; Lobo et al, 2004) This binding pocket was thought to be present in all cys-loop receptors, yet the modulatory effects of alcohols and anesthetics vary between different members of this receptor family (Dupre et al, 2007). A polyalcohol, may be able to access this cavity on the receptor
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
