Hiemke C, Jussofie A, Jüptner M
Department of Psychiatry, University of Mainz, Germany.
Psychoneuroendocrinology. 1991;16(6):517-23. doi: 10.1016/0306-4530(91)90035-r.
3 alpha-Hydroxy-5 alpha-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 GABAA receptor binding, by determining the allosteric properties of HPO on the in vitro binding of 3H-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 3H-muscimol to GABAA 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 GABAA receptor binding provide evidence that this pregnane steroid might be a physiologically relevant modulator of GABAergic neurotransmission.
3α-羟基-5α-孕烷-20-酮（HPO）是一种孕酮代谢产物，在高浓度时通过与γ-氨基丁酸（GABA）受体相互作用而表现出麻醉特性。本研究通过测定HPO对3H-蝇蕈醇与去卵巢大鼠小脑膜组分体外结合的变构性质，来表征HPO对GABAA受体结合的低剂量效应。一种新开发的组织制备方法被用于洗脱干扰测定的内源性配体。在亚纳摩尔（0.1 nM）HPO浓度下，HPO使3H-蝇蕈醇对GABAA受体位点的亲和力降低了52%，并使可及结合位点的数量从5.5±0.5增加到7.5±1.3 pmol/mg蛋白质。HPO对GABAA受体结合的调节作用提供了证据，表明这种孕烷类固醇可能是GABA能神经传递的生理相关调节剂。
