Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons

@article{Majewska1988NeurosteroidPS,
  title={Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons},
  author={Maria Dorota Majewska and J. M. Mienville and Stefano Vicini},
  journal={Neuroscience Letters},
  year={1988},
  volume={90},
  pages={279-284}
}
Our earlier biochemical studies suggested that the neurosteroid pregnenolone sulfate (PS) may reduce gamma-aminobutyric acid (GABA) action at the Cl- channel associated with GABAA receptors. In the present electrophysiological study the interaction of PS with the GABAA receptor was tested, using whole-cell voltage-clamp recordings from isolated cerebral cortical neurons of neonatal rats. At micromolar concentrations PS reversibly inhibited GABA-induced current, behaving as an allosteric… Expand
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The neurosteroid dehydroepiandrosterone sulfate is an allosteric antagonist of the GABAA receptor
TLDR
In cultured neurons from ventral mesencephalon, DHEAS reversibly blocked GABA-induced currents, behaving as an allosteric antagonist of the GABAA receptor. Expand
Pregnenolone sulfate antagonizes GABAA receptor-mediated currents via a reduction of channel opening frequency
TLDR
The effects of PS, picrotoxin (PTX) and pentobarbital were tested on GABA-activated single Cl- channels recorded from membrane patches of rat cortical neurons in primary cultures, suggesting that PS and PTX may antagonize GABAA receptor function through the same mechanism and/or the same binding site. Expand
Endogenous neurosteroids pregnanolone and pregnanolone sulfate potentiate presynaptic glutamate release through distinct mechanisms
TLDR
A novel presynaptic effect of neurosteroids PA and PA-S to potentiate glutamate release downstream of presynptic Ca2+ influx is described; the mechanism of action of PA, but not of PA- S, partly overlaps with that of PDBu. Expand
Competitive inhibition of the glycine-induced current by pregnenolone sulfate in cultured chick spinal cord neurons
TLDR
The effect of the neurosteroid pregnenolone sulfate on the glycine receptor-mediated response was studied in cultured chick spinal cord neurons using the whole-cell voltage-clamp recording technique and indicates that PS does not act as an open-channel blocker. Expand
Pregnenolone sulfate increases the convulsant potency of N-methyl-D-aspartate in mice.
TLDR
It is found that pregnenolone sulfate significantly increased the convulsant potency of N-methyl-D-aspartate (NMDA), but not of pentylenetetrazol (PTZ). Expand
Neurosteroids and Extrasynaptic GABAA Receptors
Steroid sex hormones are generally thought to act through intracellular receptors, where they regulate gene expression and protein synthesis, an effect that takes minutes to hours to occur. However,… Expand
A presynaptic action of the neurosteroid pregnenolone sulfate on GABAergic synaptic transmission.
TLDR
Concentrations of PS, similar to those endogenous in the hippocampus, inhibit GABAergic synaptic transmission by a presynaptic effect and improves the understanding of the physiological function of PS. Expand
Interaction among alfaxalone, pregnenolone sulfate, and two GABAA agonists on hippocampal slices
TLDR
The results confirm the possibility that there might be differences in the interaction between GABAA agonists and modulatory steroids, and lower doses of pregnenolone sulfate at shorter incubation periods are able to inhibit the effects produced by single doses of 3-APS. Expand
Neurosteroid modulation of native and recombinant GABAA receptors
TLDR
The molecular mechanism of action of such steroids and attempts to define the steroid binding site on the receptor protein are described and the therapeutic potential of such neurosteroids is discussed. Expand
Pregnenolone sulfate modulates glycinergic transmission in rat medullary dorsal horn neurons.
TLDR
The PS-mediated modulation of glycinergic synaptic transmission might have a broad impact on the excitability of medullary dorsal horn neurons and therefore affect the processing of nociceptive transmission from orofacial tissues. Expand
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