Fleischmann A, Makman M H, Etgen A M
Dept of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Life Sci. 1995;56(20):1665-78. doi: 10.1016/0024-3205(95)98573-x.
The effect of GABA receptor agonists on release in vitro of radiolabeled GABA and glutamate was studied using a crude preparation of isolated nerve terminals (neurosomes). GABA agonists were incubated (2 min, 37 degrees C) with neurosomes prepared from hypothalamus, preoptic area (POA) and frontal cortex tissues. Under these conditions, GABA and the GABAA receptor agonist muscimol, but not the GABAB receptor agonist baclofen, stimulated 3H-GABA and 3H-glutamate release from POA but not hypothalamic or cortical neurosomes of gonadally intact male rats. These effects were inhibited by the GABAA receptor antagonists picrotoxin, bicuculline and SR-95531. Significant efflux of 3H-glutamate could be elicited from cortical neurosomes following longer (5 min) incubations with 500 microM GABA and 400 microM muscimol. Muscimol-induced release of 3H-glutamate and 3H-GABA was dependent on extracellular calcium. Muscimol and GABA failed to release 3H-GABA or 3H-glutamate from POA neurosomes of ovariectomized female rats. However, administration of estradiol and progesterone to ovariectomized females prior to sacrifice caused the appearance of muscimol induced-release of amino acids from POA neurosomes comparable to that obtained in male rats. GABA-induced release of 3H-glutamate was similarly dependent on pretreatment of ovariectomized rats with ovarian steroids. GABAA receptor-induced release of amino acids is therefore brain region-specific and modified by hormonal status.
利用分离的神经末梢（神经小体）粗制品，研究了γ-氨基丁酸（GABA）受体激动剂对放射性标记的GABA和谷氨酸体外释放的影响。将GABA激动剂与由下丘脑、视前区（POA）和额叶皮质组织制备的神经小体一起孵育（2分钟，37摄氏度）。在这些条件下，GABA和GABAA受体激动剂蝇蕈醇，但不是GABAB受体激动剂巴氯芬，刺激了来自性腺完整雄性大鼠POA而非下丘脑或皮质神经小体的3H-GABA和3H-谷氨酸释放。这些作用被GABAA受体拮抗剂印防己毒素、荷包牡丹碱和SR-95531抑制。在用500微摩尔GABA和400微摩尔蝇蕈醇进行更长时间（5分钟）孵育后，可从皮质神经小体中引发显著的3H-谷氨酸外流。蝇蕈醇诱导的3H-谷氨酸和3H-GABA释放依赖于细胞外钙。蝇蕈醇和GABA未能从去卵巢雌性大鼠的POA神经小体中释放3H-GABA或3H-谷氨酸。然而，在处死前给去卵巢雌性大鼠注射雌二醇和孕酮，导致蝇蕈醇诱导的POA神经小体氨基酸释放出现，与雄性大鼠中获得的情况相当。GABA诱导的3H-谷氨酸释放同样依赖于用卵巢类固醇对去卵巢大鼠进行预处理。因此，GABAA受体诱导的氨基酸释放具有脑区特异性，并受激素状态的影响。
