Decrease in the Function of the γ‐Aminobutyric Acid‐Coupled Chloride Channel Produced by the Repeated Administration of Pentylenetetrazol to Rats
Decrease in the Function of the γ‐Aminobutyric Acid‐Coupled Chloride Channel Produced by the Repeated Administration of Pentylenetetrazol to Rats
复制标题
反复给予大鼠戊四唑导致γ-氨基丁酸偶联氯离子通道功能下降
作者：
M. Corda;O. Giorgi;B. Longoni;M. Orlandi;G. Biggio
摘要：戊四唑(PTZ；25-75 mg/kg，i.p.)急性给药未能修饰T-[35S]丁基二环磷硫酸盐([35S]Tbps)与大鼠大脑皮层膜制剂的特异性结合。相反，重复给药PTZ(30 mg/kg，每周三次，持续12周)在不改变解离常数的情况下，降低了26%的[33S]Tbps结合位点密度。在最后一次PTZ给药后3天观察这一效果。在最后一次注射后3天，PTZ处理的大鼠大脑皮层对7-氨基丁酸刺激的~(36)CI-−摄取也有平行的减少。重复给予PTZ会对药物或化学点燃产生敏化。事实上，在治疗的第一周没有观察到惊厥，但到了第12周，所有的动物都对PTZ变得敏感。这一结果与以下假设一致：长期服用亚惊厥剂量的PTZ会导致GABA偶联氯通道活性降低，这可能与该化合物产生的化学点燃有关。
Abstract: The acute administration of pentylenetetrazol (PTZ; 25–75 mg/kg i.p.) failed to modify the specific binding of t‐[35S]butylbicyclophosphorothionate ([35S]TBPS) to membrane preparations from the cerebral cortex of the rat. In contrast, the repeated administration of PTZ (30 mg/kg i.p., three times a week for 12 weeks) reduced by 26% the density of [33S]TBPS binding sites without modifying the dissociation constant. This effect was observed 3 days after the last PTZ administration. A parallel reduction of 7‐amino‐butyric acid (GABA)‐stimulated 36CI− uptake was measured in the cerebral cortex of PTZ‐treated rats 3 days after the last injection. The repeated administration of PTZ produced sensitization to the drug, or chemical kindling. In fact, no convulsions were observed in the first week of treatment, but all the animals became sensitized to PTZ by the 12th week. The results are consistent with the hypothesis that chronic treatment with PTZ at a subconvulsant dose causes a decrease in GABA‐coupled chloride channel activity that may be related to the chemical kindling produced by this compound.
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影响因子：
5
作者：
RAMANJANEYULU, R;TICKU, MK
通讯作者：
TICKU, MK
苯二氮卓受体配体对氯离子载体的调节：γ-氨基丁酸和配体功效的影响。
影响因子：
3.6
作者：
Gee,KW;Lawrence,LJ;Yamamura,HI
通讯作者：
Yamamura,HI
影响因子：
3.6
作者：
R. Squires;J. Casida;M. Richardson;E. Saederup
通讯作者：
R. Squires;J. Casida;M. Richardson;E. Saederup
γ-氨基丁酸激动剂和拮抗剂改变穿过脑膜的氯离子通量。
影响因子：
3.6
作者：
Allan,AM;Harris,RA
通讯作者：
Harris,RA