Tominaga Koji, Kai Mamiko, Yamauchi Atsushi, Dohgu Shinya, Toda Kayoko, Oishi Ryozo, Kataoka Yasufumi
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan, 814-0180, Fukuoka, Japan.
Life Sci. 2002 Dec 20;72(4-5):425-30. doi: 10.1016/s0024-3205(02)02272-5.
In this study, we investigated the effect of cyclosporin A on the binding properties of the GABAA receptor in the hippocampus, known to be responsible for the induction of seizures, to clarify the mechanism of cyclosporin A-inhibited GABA neurotransmission in ovariectomized rats, as a climacterium model. The effects of single and subchronic treatments with cyclosporin A were examined on [3H]muscimol binding to hippocampal synaptosomal membranes in sham, ovariectomized, and estradiol/ovariectomized rats. A single treatment with cyclosporin A (40 mg/kg, i.p.) failed to change [3H]muscimol binding in the 3 groups, when compared with each corresponding vehicle-treated group. Subchronic treatment with cyclosporin A (40 mg/kg, i.p., once a day for 5 days) significantly decreased the amount of [3H]muscimol binding in ovariectomized rats. However, this inhibitory effect was not observed in sham or estradiol/ovariectomized rats. These results demonstrated that the binding activity of the GABAA receptor was decreased in ovariectomized rats after subchronic cyclosporin A treatment. This study supports the hypothesis that ovariectomy elevates the susceptibility to cyclosporin A-induced convulsions by accelerating the inhibitory actions of cyclosporin A on GABA neurotransmission in the hippocampus.
在本研究中，我们调查了环孢素A对海马中γ-氨基丁酸A（GABAA）受体结合特性的影响，已知该受体与癫痫发作的诱导有关，以阐明环孢素A抑制去卵巢大鼠（作为更年期模型）GABA神经传递的机制。研究了环孢素A单次和亚慢性处理对假手术组、去卵巢组和雌二醇/去卵巢组大鼠海马突触体膜上[3H]蝇蕈醇结合的影响。与相应的溶剂处理组相比，环孢素A单次处理（40mg/kg，腹腔注射）未能改变三组中[3H]蝇蕈醇的结合。环孢素A亚慢性处理（40mg/kg，腹腔注射，每天一次，共5天）显著降低了去卵巢大鼠中[3H]蝇蕈醇的结合量。然而，在假手术组或雌二醇/去卵巢组大鼠中未观察到这种抑制作用。这些结果表明，亚慢性环孢素A处理后，去卵巢大鼠中GABAA受体的结合活性降低。本研究支持以下假设：去卵巢通过加速环孢素A对海马中GABA神经传递的抑制作用，提高了对环孢素A诱导惊厥的易感性。
