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Rapid non‐genomic effect of glucocorticoid metabolites and neurosteroids on the γ‐aminobutyric acid‐A receptor
Author(s) -
Strömberg J.,
Bäckström T.,
Lundgren P.
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04047.x
Subject(s) - allopregnanolone , neuroactive steroid , chemistry , glucocorticoid , gabaa receptor , endocrinology , pregnanolone , medicine , glucocorticoid receptor , gamma aminobutyric acid , receptor , pharmacology , biochemistry , biology
Glucocorticoids and neurosteroids, such as allopregnanolone and tetrahydrodeoxycorticosterone, are released during stress. A non‐genomic effect of glucocorticoids has been established but is not yet fully understood. We have studied the effect of glucocorticoid metabolites on the γ‐aminobutyric acid (GABA) system. In these experiments we studied the effects of the glucocorticoid metabolites allotetrahydrocortisol, tetrahydrocortisol, allotetrahydrocortisone and tetrahydrocortisone in rat cortical microsacs. Our results showed that both these cortisol and cortisone metabolites reduce GABA‐mediated chloride ion uptake. This reduction was not observed in the presence of allopregnanolone but allotetrahydrocortisol interacts with allopregnanolone, enhancing the allopregnanolone‐stimulated potentiation of GABA‐mediated chloride ion uptake. This enhanced effect was completely blocked by the addition of 30 µ m of the 3β‐isomer of allopregnanolone, isoallopregnanolone. Our findings show that steroids released during stress interact with each other and GABA in the GABA system.