Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons

  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},

Potentiation of GABA-induced inhibition by 20-hydroxyecdysone, a neurosteroid, in cultured rat cortical neurons.

The results suggest that 20-HE acts on the modulatory site of the GABAA receptor and potentiates GABAergic inhibition in rat cortical neurons.

Neurosteroids and Extrasynaptic GABAA Receptors

The synthesis, action and the activity of neurosteroids on synaptic and extrasynaptic GABAA receptors are reviewed.

A presynaptic action of the neurosteroid pregnenolone sulfate on GABAergic synaptic transmission.

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.

Neurosteroid modulation of native and recombinant GABAA receptors

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.

Pregnenolone sulfate modulates glycinergic transmission in rat medullary dorsal horn neurons.

Inhibition by pregnenolone sulphate, a metabolite of the neurosteroid pregnenolone, of voltage-gated sodium channels expressed in Xenopus oocytes.

It is suggested that pregnenolone sulphate, a metabolite of pregnanolone, suppresses the function of Na(v) via increased inactivation, which may contribute to the neuroprotection.



Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.

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.

Prolongation of hippocampal inhibitory postsynaptic potentials by barbiturates

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.

Internal perfusion studies demonstrating GABA-induced chloride responses in frog primary afferent neurons.

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.

Voltage‐clamp analysis of somatic gamma‐aminobutyric acid responses in adult rat hippocampal CA1 neurones in vitro.

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.

Pregnenolone and its sulfate ester in the rat brain

The presence of an adrenodoxin-like ferredoxin and cytochrome P-450 in brain mitochondria.

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.