DUAL MECHANISMS OF GABA(A) RESPONSE-INHIBITION BY BETA-LACTAM ANTIBIOTICS IN THE PYRAMIDAL NEURONS OF THE RAT CEREBRAL-CORTEX
DUAL MECHANISMS OF GABA(A) RESPONSE-INHIBITION BY BETA-LACTAM ANTIBIOTICS IN THE PYRAMIDAL NEURONS OF THE RAT CEREBRAL-CORTEX
复制标题
DOI：
10.1111/j.1476-5381.1995.tb15957.x
复制
发表时间：
1995-12-01
影响因子：
7.3
通讯作者：
AKAIKE, N
中科院分区：
文献类型：
--
作者：
FUJIMOTO, M;MUNAKATA, M;AKAIKE, N
1在电压钳条件下，采用制霉菌素穿孔膜片记录方法，观察β-内酰胺类抗生素对大鼠额叶皮质新鲜分离锥体神经元上γ-氨基丁酸(GABA)诱导的氯电流的影响。2在-40 mV的保持电位下，GABA诱导的内向电流呈浓度依赖性增加，EC(50)为6.7×10(-6)M。3所有的β-内酰胺类药物(青霉素、亚胺培南、氨曲南和头孢替安)均以浓度依赖的方式抑制10(-5)M的GABA诱导的反应，IC50和Hill系数分别为1.3×10(-3)M和0.64，亚胺培南为9.6×10(-4)M和0.83，2.5×10(-3)M和9.99。4亚胺培南竞争性抑制GABA(A)受体，而青霉素以非竞争性方式抑制GABA(A)受体。5亚胺培南的抑制作用不呈电压依赖性，而青霉素的抑制作用呈电压依赖性。
1 The effects of beta-lactam antibiotics on the gamma-aminobutyric acid (GABA)-induced Cl- current were investigated in pyramidal neurones freshly dissociated from the rat frontal cortex by the use of a nystatin-perforated patch recording mode under voltage-clamp conditions.2 The GABA-induced inward current increased in a concentration-dependent manner with an EC(50) of 6.7 x 10(-6) M at a holding potential of -40 mV. The GABA response was accompanied by an increase in the membrane conductance and reversed at near the Cl- equilibrium potential.3 All beta-lactams (penicillin, imipenem, aztreonam and cefotiam) inhibited the 10(-5) M GABA-induced response in a concentration-dependent manner with an IC50 and Hill coefficient of 1.3 x 10(-3) M and 0.64 for penicillin, 9.6 x 10(-4) M and 0.83 for imipenem, 2.5 x 10(-3) M and 9.99 for aztreonam, and 2.9 x 10(-4) M and 1.03 for cefotiam.4 Imipenem inhibited the GABA-response competitively while penicillin inhibited the same response in a noncompetitive fashion.5 The inhibitory action of imipenem showed no voltage-dependency, whereas the effect of penicillin was voltage-dependent.6 It is thus proposed that some classes of beta-lactams, including imipenem, may have a mechanism that is different from penicillin and competitively affects the GABA(A) receptor.