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
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
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 16 REFERENCES
Pregnenolone-sulfate: an endogenous antagonist of the γ-aminobutyric acid receptor complex in brain?
TLDR
The interaction of the 'neurosteroid', pregnenolone-sulfate (PS), with the GABA/benzodiazepine/chloride ionophore receptor complex was investigated in rat brain subcellular preparations, suggesting the regulation of GABAergic neurotransmission by various neurosteroids may be an important mechanism for controlling neuronal excitability. Expand
Glucocorticoids are modulators of GABAA receptors in brain
TLDR
Nanomolar concentrations of corticosterone and pregnenolone-sulfate, but not dexamethasone, enhanced muscimol binding in brain regions that were characterized by reduced binding following Adx, which was due to enhanced affinities of GABA receptors. Expand
Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.
TLDR
Two metabolites of the steroid hormones progesterone and deoxycorticosterone are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons, which may explain the ability of certain steroid hormones to rapidly alter neuronal excitability. Expand
Antagonists of gaba responses, studied using internally perfused frog dorsal root ganglion neurons
TLDR
GA responses on frog dorsal root ganglion cell were depressed by a variety of other metal ions and bicuculline and the heavy metal ions appear to block at or very near to the agonist binding site, while penicillin probably blocks the ion channel. Expand
Prolongation of hippocampal inhibitory postsynaptic potentials by barbiturates
TLDR
It is found that barbiturates hyperpolarise hippocampal neurones and markedly prolong the i.p.s. by a direct action on inhibitory synapses, anaesthetic doses increasing the duration fivefold. Expand
Internal perfusion studies demonstrating GABA-induced chloride responses in frog primary afferent neurons.
TLDR
The reversal potential of GABA-induced Cl- response (EGABA) was equal to Cl- equilibrium potential (ECl) and behaved as a simple Cl- electrode following changes of external and internal Cl- concentrations, which indicate the adequacy of internal perfusion. Expand
Structure-activity relationships for steroid interaction with the gamma-aminobutyric acidA receptor complex.
TLDR
Comparison of the structure-activity relationship data obtained in this study with those for steroid-induced general anesthesia strongly suggests that steroidal anesthesia may result from the interaction between steroids and the GABAA receptor. Expand
Voltage‐clamp analysis of somatic gamma‐aminobutyric acid responses in adult rat hippocampal CA1 neurones in vitro.
TLDR
The response of CA1 pyramidal neurones to somatic application of gamma‐aminobutyric acid (GABA) was studied in adult hippocampal slices using single‐electrode voltage‐clamp techniques and outward rectification of the response was observed. Expand
Pregnenolone and its sulfate ester in the rat brain
TLDR
Brain P and PS levels did not seem to depend on steroidogenic gland secretion: no meaningful difference occurred in brain 15 days after adrenalectomy plus orchiectomy, compared with sham-operated controls and it is proposed that P andPS formation or accumulation in the rat brain depend on in situ mechanisms unrelated to the peripheral endocrine gland system. Expand
The presence of an adrenodoxin-like ferredoxin and cytochrome P-450 in brain mitochondria.
TLDR
An iron-sulfur protein has been isolated from bovine brain mitochondria and purified 200-fold and indicates that the isolated ferredoxin is part of a cytochrome P-450-dependent hydroxylation system. Expand
...
1
2
...