Oxytocin regulates neurosteroid modulation of GABA(A) receptors in supraoptic nucleus around parturition

In this study, we investigate how neurosteroid sensitivity of GABA(A) receptors (GABA(A)Rs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABA(A)Rs become insensitive to the neurosteroid allopregnanolone attributabl...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-02, Vol.23 (3), p.788-797
Main Authors: Koksma, Jan-Jurjen, van Kesteren, Ronald E, Rosahl, Thomas W, Zwart, Ruud, Smit, August B, Lüddens, Hartmut, Brussaard, Arjen B
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics
Cell Line
Female
gamma-Aminobutyric Acid - pharmacology
Humans
Kidney - cytology
Kidney - metabolism
Ligands
Male
Mice
Mice, Knockout
Mice, Transgenic
Oocytes - metabolism
Oxytocin - metabolism
Oxytocin - pharmacology
Patch-Clamp Techniques
Phosphoprotein Phosphatases - metabolism
Pregnancy
Pregnanolone - pharmacology
Protein Kinase C - metabolism
Rats
Rats, Wistar
Receptors, GABA-A - drug effects
Receptors, GABA-A - genetics
Receptors, GABA-A - metabolism
Steroids - pharmacology
Supraoptic Nucleus - drug effects
Supraoptic Nucleus - metabolism
Transfection
Xenopus
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Summary:In this study, we investigate how neurosteroid sensitivity of GABA(A) receptors (GABA(A)Rs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABA(A)Rs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABA(A)Rs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABA(A)Rs from a neurosteroid-sensitive mode toward a condition in which the receptors are not sensitive. This indicates that there may be an inverse causal relationship between the extent to which the GABA(A)R or one of its interacting proteins is phosphorylated and the neurosteroid sensitivity of the GABA(A)R. Neurosteroid sensitivity was not affected by changes in subunit composition of GABA(A)Rs known to occur concurrently in these cells.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.23-03-00788.2003