These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Allosteric effects of a GABA receptor-active steroid are altered by stress.
    Author: Deutsch SI, Park CH, Hitri A.
    Journal: Pharmacol Biochem Behav; 1994 Apr; 47(4):913-7. PubMed ID: 8029262.
    Abstract:
    Recently, ring A reduced metabolites of naturally occurring steroids have been shown to act as allosteric modulators of GABA-gated chloride ion conductance. Specifically, 5 alpha-pregnane-3 alpha,21-diol-20-one (allotetrahydrodeoxycorticosterone; 5 alpha-THDOC) was shown to be a positive allosteric effector. For example, 5 alpha-THDOC enhances the specific binding of [3H]flunitrazepam, a benzodiazepine receptor agonist, among other pharmacological actions. Swim stress has been shown to reduce the ability of flurazepam, a prototypic benzodiazepine agonist, to antagonize the electrical precipitation of tonic hindlimb extension in mice. This stress-induced reduction in flurazepam's antiseizure efficacy persists for up to 72 h and is associated with alterations in the specific binding of ligands to the GABAA receptor complex. In the current study, the potentiation of [3H]flunitrazepam binding by 5 alpha-THDOC was greater in cerebral cortical membranes prepared from stressed mice compared with unstressed controls. Moreover, nanomolar concentrations of 5 alpha-THDOC that were ineffective in potentiating the specific binding of [35S]TBPS in cerebral cortical membranes prepared from unstressed control mice were capable of potentiating this binding in membranes prepared from stressed animals. Specifically, 50 nM 5 alpha-THDOC caused a 23% increase in the specific binding of [35S]TBPS in membranes from stressed mice, whereas it was without any significant effect in unstressed controls. This apparent ability of 5 alpha-THDOC to distinguish between the binding of [35S]TBPS to crude membranes prepared from stressed and unstressed control mice was eliminated in the presence of a 5 microM concentration of GABA.(ABSTRACT TRUNCATED AT 250 WORDS)
    [Abstract] [Full Text] [Related] [New Search]