Phenol-induced neurotoxicity manifests as twitching/tremor and convulsions, but its molecular mechanisms underlying the behavioral responses remain unclear. We assessed the role of the brain Cl-/HCO3--ATPase in behavioral responses in rats following an in vivo intraperitoneal injection of phenol (20-160 mg/kg). Low concentrations of phenol (20-80 mg/kg) increased the ATPase activity as well as the head twitching responses in rat, whereas higher phenol concentrations (>60 mg/kg) increased the tremor but reduced the ATPase activity. At phenol concentrations >120 mg/kg, no ATPase activity was detected. Phenobarbital (10 mg/kg) and picrotoxin (1 mg/kg) as well as o-vanadate (2 mg/kg), significantly prevented (˜55-70%) the phenol-induced change in the behavioral responses and completely restored the enzyme activity. In vitro experiments confirmed that phenol stimulated the Cl-/HCO3--ATPase activity at low concentrations, but had no stimulating effect on other transport ATPases. Low doses of phenol increased the formation of phosphoprotein and the rate of ATP-consuming Cl- transport by the reconstituted enzyme. The present findings provide evidence that phenol-induced neurotoxicity involves the Cl-/HCO3--ATPase in the behavioral responses in mammals and indicate the potential benefit of this enzyme as a target for the treatment of head twitching and other types of tremor diseases.

中文翻译：

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脑GABAAR偶联的Cl- / HCO3--ATPase参与酚引起的大鼠头部抽搐和震颤反应。

苯酚引起的神经毒性表现为抽搐/震颤和抽搐，但其行为反应基础的分子机制仍不清楚。在体内腹膜内注射苯酚（20-160 mg / kg）后，我们评估了脑Cl- / HCO3--ATPase在大鼠行为反应中的作用。低浓度的苯酚（20-80 mg / kg）增加了大鼠的ATPase活性以及头部抽搐反应，而较高的苯酚浓度（> 60 mg / kg）增加了震颤但降低了ATPase活性。在苯酚浓度> 120 mg / kg时，未检测到ATPase活性。苯巴比妥（10 mg / kg）和微毒素（1 mg / kg）以及邻钒酸盐（2 mg / kg）可以显着防止（〜55-70％）苯酚引起的行为反应变化，并完全恢复酶活性。体外实验证实，苯酚在低浓度下会刺激Cl- / HCO3--ATPase活性，但对其他转运ATPase没有刺激作用。低剂量的苯酚会增加磷蛋白的形成，并增加重组酶消耗ATP的Cl转运的速率。本发现提供了证据，表明苯酚诱导的神经毒性在哺乳动物的行为反应中涉及Cl- / HCO3--ATPase，并表明该酶作为治疗头部抽搐和其他类型的震颤疾病的靶标的潜在益处。