Potentiation of glycine responses by dideoxyforskolin and tamoxifen in rat spinal neurons

Chesnoy-Marchais, Dominique

doi:10.1046/j.1460-9568.2003.02481.x

Cited by 10 publications

(7 citation statements)

References 93 publications

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“…The half-effective concentration of glycine (EC 50 ) estimated from the dose–response curve was in the range 40–70 μM (data not shown), which corresponds closely to previously reported values in cell lines expressing α1 GlyR (Fucile et al, 1999, 2000; Buldakova et al, 2007; Markova et al, 2008). These values are also similar to those reported for acutely isolated rat hippocampal neurons (Kondratskaya et al, 2002) and for other preparations (Chesnoy-Marchais, 2003; Ge et al, 2007). …”

Section: Resultssupporting

confidence: 90%

Frequency-Dependent Cannabinoid Receptor-Independent Modulation of Glycine Receptors by Endocannabinoid 2-AG

Lozovaya

Mukhtarov

Tsintsadze

et al. 2011

Front. Mol. Neurosci.

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Endocannabinoids are known as retrograde messengers, being released from the postsynaptic neuron and acting on specific presynaptic G-protein-coupled cannabinoid (CB) receptors to decrease neurotransmitter release. Also, at physiologically relevant concentrations cannabinoids can directly modulate the function of voltage-gated and receptor-operated ion channels. Using patch-clamp recording we analyzed the consequences of the direct action of an endocannabinoid, 2-arachidonoylglycerol (2-AG), on the functional properties of glycine receptor channels (GlyRs) and ionic currents in glycinergic synapses. At physiologically relevant concentrations (0.1–1 μM), 2-AG directly affected the functions of recombinant homomeric α1H GlyR: it inhibited peak amplitude and dramatically enhanced desensitization. The action of 2-AG on GlyR-mediated currents developed rapidly, within ∼300 ms. Addition of 1 μM 2-AG strongly facilitated the depression of glycine-induced currents during repetitive (4–10 Hz) application of short (2 ms duration) pulses of glycine to outside-out patches. In brainstem slices from CB1 receptor knockout mice, 2-AG significantly decreased the extent of facilitation of synaptic currents in hypoglossal motoneurons during repetitive (10–20 Hz) stimulation. These observations suggest that endocannabinoids can modulate postsynaptic metaplasticity of glycinergic synaptic currents in a CB1 receptor-independent manner.

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Section: Resultssupporting

confidence: 90%

Frequency-Dependent Cannabinoid Receptor-Independent Modulation of Glycine Receptors by Endocannabinoid 2-AG

Lozovaya

Mukhtarov

Tsintsadze

et al. 2011

Front. Mol. Neurosci.

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“…If oestradiol increased the glycine‐sensitivity of glycine receptors as tamoxifen does (27), it might also increase the frequency of glycine release by facilitating the activity of excitatory presynaptic glycine receptors, as proposed for tamoxifen (28). This hypothesis (not yet tested with appropriate very fast perfusion of isolated neurones) does not appear to be the most likely one because oestradiol often increased the frequency of glycinergic miniatures without affecting their amplitude.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, possible effects of oestradiol on glycinergic neurotransmission have not yet been investigated. Recently, the oestrogen receptor modulator tamoxifen was shown to potentiate chloride responses to low concentrations of glycine or GABA in cultured spinal neurones (27) and to enhance the inhibitory glycinergic synaptic transmission in rat brainstem slices (28). As expected from its potentiating effect on glycine receptors, tamoxifen increased the amplitude of glycinergic miniature synaptic currents recorded after blockade of action potentials by tetrodotoxin (TTX).…”

mentioning

confidence: 99%

Oestradiol Rapidly Enhances Spontaneous Glycinergic Synaptic Inhibition of Hypoglossal Motoneurones

Chesnoy-Marchais

Meillerais

2007

J Neuroendocrinology

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Whereas oestradiol is well-known to facilitate excitatory glutamatergic synaptic transmission, its effects on fast inhibitory neurotransmission are not as well established. Possible acute modulation of the spontaneous glycinergic synaptic activity by oestradiol was investigated in voltage-clamped hypoglossal motoneurones by whole-cell patch-clamp recording in rat brainstem slices. The spontaneous glycinergic synaptic activity was continuously recorded in each neurone under control conditions, during 12-20 min of perfusion with 17beta-oestradiol and during washing. When oestradiol was diluted in ethanol, the control solution contained the same amount of ethanol. At 100 nM, oestradiol markedly increased the frequency of the total spontaneous glycinergic activity. Similar experiments were performed after blockade of action potentials by tetrodotoxin, aiming to isolate miniature glycinergic synaptic currents. Oestradiol increased the frequency of glycinergic miniatures in most slices, in some cases within less than 1 min. In some slices, oestradiol also favoured the occurrence of glycinergic miniatures of large amplitude. These effects were slowly reversible during washing. At 1 nm, oestradiol still increased the frequency of glycinergic miniatures. The results were confirmed in the absence of ethanol by using water-soluble cyclodextrin-encapsulated oestradiol. In these experiments, the control solution contained the same amount of (2-hydroxypropyl)-beta-cyclodextrin as the oestradiol-containing solution. In addition, prolonged control recordings were performed without applying oestradiol to check the stability of the glycinergic synaptic activity during prolonged whole-cell recordings. The results show, for the first time, that, within a few minutes, oestradiol can enhance the spontaneous synaptic release of a major inhibitory transmitter, glycine.

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“…When applied at concentrations of 0.2 -5 M, it strongly potentiated submaximal GlyR responses in cultured spinal neurons by inducing a leftward shift in the glycine EC 50 value [160]. When applied at concentrations of 0.2 -5 M, it strongly potentiated submaximal GlyR responses in cultured spinal neurons by inducing a leftward shift in the glycine EC 50 value [160].…”

Section: Tamoxifenmentioning

confidence: 96%

“…At low micromolar concentrations, it increases the magnitude of submaximal glycine-gated currents in cultured spinal neurons [160]. At low micromolar concentrations, it increases the magnitude of submaximal glycine-gated currents in cultured spinal neurons [160].…”

Section: Dideoxyforskolinmentioning

confidence: 98%

Molecular Pharmacology of the Glycine Receptor Chloride Channel

Webb

Lynch

2007

CPD

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The glycine receptor (GlyR) Cl(-) channel belongs to the cysteine-loop family of ligand-gated ion channel receptors. It is best known for mediating inhibitory neurotransmission in motor and sensory reflex circuits of the spinal cord, although glycinergic synapses are also present in the brain stem, cerebellum and retina. Extrasynaptic GlyRs are widely distributed throughout the central nervous system and they are also found in sperm and macrophages. A total of 5 GlyR subunits (alpha1-4 and beta) have been identified. Embryonic receptors comprise alpha2 homomers whereas adult receptors comprise predominantly alpha beta heteromers in a 2:3 stoichiometry. Notably, the alpha3 subunit is present in synaptic GlyRs that mediate inhibitory neurotransmission onto spinal nociceptive neurons. These receptors are specifically inhibited by inflammatory mediators, implying a role for alpha3-containing GlyRs in inflammatory pain sensitisation. Because molecules that increase GlyR current may have clinical potential as muscle relaxant and peripheral analgesic drugs, this review focuses on the molecular pharmacology of GlyR potentiating substances. Of all GlyR potentiating substances identified to date, we conclude that 5HT(3)R antagonists such as tropisetron offer the most promise as therapeutic lead compounds. However, one problem is that that virtually all known GlyR potentiating compounds, including tropisetron analogues, lack specificity for the GlyR. Another is that almost nothing is known about the pharmacological properties of alpha3-containing GlyRs, which is the subtype of choice for targeting by novel antinociceptive agents. These issues need to be addressed before GlyR-specific therapeutics can be developed.

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Potentiation of glycine responses by dideoxyforskolin and tamoxifen in rat spinal neurons

Cited by 10 publications

References 93 publications

Frequency-Dependent Cannabinoid Receptor-Independent Modulation of Glycine Receptors by Endocannabinoid 2-AG

Frequency-Dependent Cannabinoid Receptor-Independent Modulation of Glycine Receptors by Endocannabinoid 2-AG

Oestradiol Rapidly Enhances Spontaneous Glycinergic Synaptic Inhibition of Hypoglossal Motoneurones

Molecular Pharmacology of the Glycine Receptor Chloride Channel

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