Inhibition of GABAAReceptor Function by Tyrosine Kinase Inhibitors and Their Inactive Analogues

Dunne, Emma L.; Moss, Stephen J.; Smart, Trevor G.

doi:10.1006/mcne.1998.0717

Cited by 30 publications

(14 citation statements)

References 30 publications

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“…Both genistein and daidzein inhibit GABA A R (101), which is the major inhibitory receptor in the brain with roles in seizures, hyperactivity, learning and memory, and sleep/wake cycles. Alternatively, or perhaps concurrently, soy isoflavones could affect neuronal function through mGluR 5 signaling.…”

Section: Melding the Bear “Mglur Theory Of Fxs” With The Mermelstein mentioning

confidence: 99%

A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

Westmark

2014

Front. Neurol.

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Numerous neurological disorders including fragile X syndrome, Down syndrome, autism, and Alzheimer’s disease are co-morbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity, and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold.

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Section: Melding the Bear “Mglur Theory Of Fxs” With The Mermelstein mentioning

confidence: 99%

A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

Westmark

2014

Front. Neurol.

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“…tein kinase A and calmodulin kinase II is implicated in the RP (Kano et al, 1996;Kawaguchi and Hirano, 2000), it has been reported that GABA A receptors are phosphorylated by other kinases, such as protein kinase C (Fancsik et al, 2000) and tyrosine kinase (Wan et al, 1997;Dunne et al, 1998). Additional study is therefore needed to determine whether the P2YR-mediated modulation of GABA A receptor sensitivity also involves protein kinases.…”

Section: P2y 1 R-mediated Ltp Of Gabaergic Synapses Via a Postsynaptimentioning

confidence: 99%

Metabotropic P2Y Purinoceptor-Mediated Presynaptic and Postsynaptic Enhancement of Cerebellar GABAergic Transmission

Saitow¹,

Murakoshi²,

Suzuki³

et al. 2005

J. Neurosci.

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] i . The other action of P2YR agonists on cerebellar GABAergic synapses was that they produced a short-term increase in the frequency and the amplitude of spontaneous GABA A receptor-mediated IPSCs in PCs in a manner sensitive to a P2Y 1 R antagonist, N 6 -methyl 2Ј-deoxyadenosine 3Ј,5Ј-bisphosphate. This action appeared to be attributable to an excitability increase in presynaptic GABAergic interneurons, because ADP excited all Lugaro cells examined and some of interneurons in the molecular layer. These results suggest that activation of cerebellar P2Y purinoceptors leads to modulation of GABAergic transmission in different spatial and temporal domains, namely short-term and long-term plasticity through presynaptic and postsynaptic mechanisms at interneuron3PC inhibitory synapses in the rat cerebellar cortex.

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“…Receptor phosphorylation seems to play a role in the regulation and modulation of the GABA A receptor complex. Several studies have demonstrated that GABA A receptor function is regulated by phosphorylation via Ca 2ϩ /phospholipid-dependent protein kinase C (PKC) (Krishek et al, 1994;Poisbeau et al, 1999), cAMP-dependent protein kinase (PKA) (Poisbeau et al, 1999), Ca 2ϩ /calmodulin-dependent protein kinase II (McDonald and Moss, 1994), and protein tyrosine kinase (Bureau and Laschet, 1995;Moss et al, 1995;Dunne et al, 1998) and by an unidentified kinase associated with the GABA A receptor (Bureau and Laschet, 1995). Similarly, there is preliminary evidence that phosphorylation plays a role in the modulation of the GABA A receptor complex by neurosteroids (Gyenes et al, 1994;Leidenheimer and Chapell, 1997).…”

mentioning

confidence: 99%

Neurosteroid Modulation of GABA IPSCs Is Phosphorylation Dependent

Fáncsik¹,

Linn²,

Tasker

2000

J. Neurosci.

134

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The neurosteroid 3␣-hydroxy-5␣-pregnan-20-one (allopregnanolone) facilitates GABA A receptor-mediated ionic currents via allosteric modulation of the GABA A receptor. Accordingly, allopregnanolone caused an increase in the slow decay time constant of spontaneous GABA-mediated IPSCs in magnocellular neurons recorded in hypothalamic slices. The allopregnanolone effect on IPSCs was inhibited by a G-protein antagonist as well as by blocking protein kinase C and, to a lesser extent, cAMP-dependent protein kinase activities. G-protein and protein kinase C activation in the absence of the neurosteroid had no effect on spontaneous IPSCs but enhanced the effect of subsequent allopregnanolone application. These findings together suggest that the neurosteroid modulation of GABA-mediated IPSCs requires G-protein and protein kinase activation, although not via a separate G-protein-coupled steroid receptor. : hypothalamus; neurosteroid; progestin; allopregnanolone; kinase; phosphorylation; GABA A receptor; G-proteins; whole-cell recording Neuronal function is acutely modulated by a class of steroids, the neurosteroids, that are synthesized de novo in the CNS (Corpechot et al., 1993;Cheney et al., 1995;Schumacher and Baulieu, 1995). 3␣-Hydroxy-5␣-pregnan-20-one (Allopregnanolone), a progesterone metabolite, has been shown to enhance the GABA A receptor-mediated Cl Ϫ current caused by exogenously applied GABA (Majewska et al., 1986;Harrison et al., 1987;Lambert et al., 1990;Puia et al., 1993;Rupprecht et al., 1993). The modulatory efficacy of the neurosteroids seems to depend on the subunit composition of the GABA A receptor. Variations in subunit subtypes change or eliminate completely the neurosteroids' ability to modulate GABA currents (Shingai et al., 1991;Zaman et al., 1992;Puia et al., 1993;Zhu et al., 1996; Reynolds, 1998, 1999;Smith et al., 1998;Brussaard et al., 1999). Receptor phosphorylation seems to play a role in the regulation and modulation of the GABA A receptor complex. Several studies have demonstrated that GABA A receptor function is regulated by phosphorylation via Ca 2ϩ /phospholipid-dependent protein kinase C (PKC) (Krishek et al., 1994;Poisbeau et al., 1999), cAMP-dependent protein kinase (PKA) (Poisbeau et al., 1999), Ca 2ϩ /calmodulin-dependent protein kinase II (McDonald and Moss, 1994), and protein tyrosine kinase (Bureau and Laschet, 1995;Moss et al., 1995;Dunne et al., 1998) and by an unidentified kinase associated with the GABA A receptor (Bureau and Laschet, 1995). Similarly, there is preliminary evidence that phosphorylation plays a role in the modulation of the GABA A receptor complex by neurosteroids (Gyenes et al., 1994;Leidenheimer and Chapell, 1997). Key wordsNeurosteroid levels measured in the CNS and in the blood are correlated with different reproductive endocrine states (Corpechot et al., 1993(Corpechot et al., , 1997Heesch and Rogers, 1995;Palumbo et al., 1995;Bixo et al., 1997). Changes in the hypothalamic allopregnanolone level during the estrus cycle seem to serve a functionspeci...

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Inhibition of GABAAReceptor Function by Tyrosine Kinase Inhibitors and Their Inactive Analogues

Cited by 30 publications

References 30 publications

A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

Metabotropic P2Y Purinoceptor-Mediated Presynaptic and Postsynaptic Enhancement of Cerebellar GABAergic Transmission

Neurosteroid Modulation of GABA IPSCs Is Phosphorylation Dependent

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