6533b870fe1ef96bd12cf22e
RESEARCH PRODUCT
Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is a physiologically relevant modulator of GABA-ergic neurotransmission.
C. HiemkeA. JussofieM. Jüptnersubject
Endocrinology Diabetes and MetabolismMetabolitemedicine.medical_treatmentOvariectomyAllosteric regulationPregnanoloneNeurotransmissionBiologyTritiumSynaptic Transmissionchemistry.chemical_compoundEndocrinologyCerebellummedicineAnimalsBinding siteReceptorBiological PsychiatryDose-Response Relationship DrugEndocrine and Autonomic SystemsGABAA receptorMuscimolfungiPregnaneCell Membraneequipment and suppliesReceptors GABA-ARatsPsychiatry and Mental healthSteroid hormonechemistryBiochemistryFemaledescription
Abstract 3α-Hydroxy-5α-pregnan-20-one (HPO) is a progesterone metabolite which exhibits narcotic properties at high concentrations by interactions with the receptor for gamma-aminobutyric acid (GABA). The present investigation characterized low-dose effects of HPO on GABA A receptor binding, by determining the allosteric properties of HPO on the in vitro binding of 3 H-muscimol to membrane fractions from the cerebella of ovariectomized rats. A newly developed method for tissue preparation was used to wash out endogenous ligands interfering with the assay. HPO reduced the affinity of 3 H-muscimol to GABA A receptor sites by 52% and enhanced the number of accessible binding sites from 5.5±0.5 to 7.5±1.3 pmol / mg protein at subnanomolar (0.1 nM) HPO concentrations. The modulatory effects of HPO on GABA A receptor binding provide evidence that this pregnane steroid might be a physiologically relevant modulator of GABAergic neurotransmission.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1991-01-01 | Psychoneuroendocrinology |