Neurosteroids Modulate Nicotinic Receptor Function in Mouse Striatal and Thalamic Synaptosomes

  title={Neurosteroids Modulate Nicotinic Receptor Function in Mouse Striatal and Thalamic Synaptosomes},
  author={Amy E. Bullock and Amy L. Clark and Sharon R. Grady and Scott F. Robinson and B S Slobe and Michael J. Marks and Allan C. Collins},
  journal={Journal of Neurochemistry},
Abstract: Progesterone and its A‐ring reduced metabolites are allosteric activators of GABAA receptors. The studies reported here examined the effects of these steroids on brain nicotinic receptors using an 86Rb+ efflux assay that likely measures the function of α4β2‐type nicotinic receptors and [3H]dopamine release, which may be modulated by an α3‐containing nicotinic receptor. Both of the A‐ring reduced metabolites of progesterone were noncompetitive inhibitors of both assays, whereas… 

Chapter 9 Pregnane Steroids and Short-Term Neural Plasticity

GABA is the major inhibitory transmitter in the brain, and its fast effects are mediated by the GABA-A receptor, which has an extensive role in short-term neural plasticity.

Pregnane Steroids and Short-Term Neural Plasticity

The widespread distribution of these neuroactive steroids across the brain suggests an extensive role in short-term neural plasticity, and many exogenous agents alter the efficacy of GABA-A receptors.

Potential use of neurosteroids and neuroactive steroids as modulators of symptoms of depression, anxiety, and psychotic disorders

It will be profitable to search for and establish symptom‐steroid relationships, as well as pharmacological and endogenous factors that can modulate NS biosynthesis and NAS formation, to be able to use these steroids in therapy.

Neuroactive neurosteroids as endogenous effectors for the sigma1 (sigma1) receptor: pharmacological evidence and therapeutic opportunities.

The recent evidence for a common mechanism of action between neurosteroids and sigma1-receptor ligands is detailed and the potential therapeutic interests of such interaction in the physiopathology of learning and memory impairments, stress, depression and neuroprotection are focused on.

Functional antagonism of gonadal steroids at the 5-hydroxytryptamine type 3 receptor.

The present study shows that the gonadal steroids, 17beta-estradiol and progesterone, may also act as functional antagonists at the 5-hydroxytryptamine type 3 (5-HT3) receptor in whole-cell voltage-clamp recordings of HEK 293 cells stably expressing the 5 -HT3 receptor.

Bovine serum albumin enhances nicotinic acetylcholine receptor function in mouse thalamic synaptosomes

The results suggest that the removal of endogenous, inhibitory compounds is largely responsible for the rapid, potentiating action of BSA at nicotinic acetylcholine receptors expressed in the mouse thalamus.

Neuroactive steroids in neuropsychopharmacology.

Neuroactive Steroids in Anxiety and Stress

Ten animal models of anxiety and stress are described that are significantly altered by one or more groups of neuroactive steroids and their interactions with stress-induced behaviors in experimental animals and humans are reviewed.



Characterization of Nicotinic Receptor‐Mediated [3H]Dopamine Release from Synaptosomes Prepared from Mouse Striatum

It is established that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum, and this finding suggests either that more than one Nicotinic receptor regulates dopamine release or that not all agonists interact with the same receptor in an identical fashion.

Nicotinic receptor function determined by stimulation of rubidium efflux from mouse brain synaptosomes.

The results indicate that a Nicotinic-receptor-mediated ion flux can be measured in brain tissue and that the ion flux may serve as a useful functional assay for nicotinic receptors in the central nervous system.

Effects of Steroid Exposure on Ligand Binding and Functional Activities of Diverse Nicotinic Acetylcholine Receptor Subtypes

It is suggested that nAChR could be among the targets mediating physiologically relevant effects of steroid action in the nervous system with unique potencies for different steroid‐nA ChR subtype combinations.

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.

Brain region-specific effects of neuroactive steroids on the affinity and density of the GABA-binding site.

  • A. Jussofie
  • Biology
    Biological chemistry Hoppe-Seyler
  • 1993
The allosteric regulation of specific [3H]-muscimol binding by neuroactive steroids to the GABA-binding sites of membrane fractions prepared from five different brain areas was characterized in order

Anxiolytic Effect of Progesterone is Mediated by the Neurosteroid Allopregnanolone at Brain GABAA Receptors

Evidence is provided that the anxiolytic effect of PROG is not associated with an intracellular steroid receptor that initiates genomic‐mediated responses, and is consistent with a nongenomic mechanism whereby PROG is metabolized to allopregnanolone, a neuroactive steroid that potentiates GABAA receptor‐ mediated responses.

Differential Responses of Expressed Recombinant Human γ‐Aminobutyric AcidA Receptors to Neurosteroids

The ability to screen synthetic molecules using expressed human receptors that selectively contain individual subunit subtype combinations may prove to be a powerful tool in the development of therapeutic agents that act as allosteric modulators of the GABAA receptor and other neurotransmitter receptors as well.

Chronic neurosteroid treatment decreases the efficacy of benzodiazepine ligands and neurosteroids at the gamma-aminobutyric acidA receptor complex in mammalian cortical neurons.

  • R. YuM. Ticku
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1995
Findings suggest that chronic 5 alpha 3 alpha treatment produces decreased efficacy of GABA, ligands that bind to the BZ site, and neurosteroids at the GABAA-BZ receptor complex, which is heterologous in nature and involves mediation via the GabAA receptor site.

Nicotinic agonists differ in activation and desensitization of 86Rb+ efflux from mouse thalamic synaptosomes.

The observation of desensitization by both stimulating and substimulating concentrations of each agonist is consistent with the predictions of the two-state model of Katz and Thesleff.