Chetty C S, Rajanna S, Hall E, Yallapragada P R, Rajanna B
Department of Biology, Savannah State College, GA, USA.
Toxicol Lett. 1996 Sep;87(1):11-7. doi: 10.1016/0378-4274(96)03670-3.
In vitro and in vivo effects of mercury (Hg), methyl mercury (MM) and lead (Pb) on [3H]inositol 1,4,5-trisphosphate (IP3) and [3H]inositol 1,3,4,5-tetrakisphosphate (IP4) receptor binding in the Sprague-Dawley rat brain cerebellar membranes were studied. In vitro studies indicate that binding of [3H]IP3 and [3H]IP4 to cerebellar membranes was inhibited by Hg while they were stimulated by MM or Pb in a concentration-dependent manner. MM was more potent (EC50 3.4 microM) than Pb (EC50 18.2 microM) in stimulating the [3H]IP3 receptor binding activity whereas Pb (IC50 30 microM) was more potent than MM (IC50 133 microM) in stimulating the [3H]IP4 receptor binding. When the rats were treated (i.p) with Hg (5 mg/kg body wt.) or MM (5 mg/kg body wt.) or Pb (25 mg/kg body wt.) for 3 or 24 h, no significant alterations in [3H]IP3 receptor binding were observed in cerebellum and cerebral cortex. But the above treatment of Pb or MM for 3 or 24 h to rats resulted in an increase of [3H]IP4 receptor binding in the membranes of cerebral cortex. However, the rats treated with Hg (1 mg/kg body wt./day) or Pb (25 mg/kg body wt./day) for 7 days did not show any alteration in binding of [3H]IP3 to its receptors in cerebellar membranes but an increase in this receptor binding was noticed with the treatment of MM (2.5 mg/kg body wt./day) for 7 days. The cerebellum and cerebral cortex of rats with the above treatment of MM or Pb for 7 days exhibited an increase in [3H]IP4 receptor binding. These in vitro and in vivo data suggest that alterations in inositol polyphosphate receptor binding by metals could result in alterations in intracellular calcium levels which may influence neuronal activity.
研究了汞（Hg）、甲基汞（MM）和铅（Pb）对Sprague-Dawley大鼠脑海马体膜中[3H]肌醇1,4,5-三磷酸（IP3）和[3H]肌醇1,3,4,5-四磷酸（IP4）受体结合的体外和体内效应。体外研究表明，Hg抑制[3H]IP3和[3H]IP4与海马体膜的结合，而MM或Pb则以浓度依赖的方式刺激这种结合。在刺激[3H]IP3受体结合活性方面，MM（EC50 3.4 microM）比Pb（EC50 18.2 microM）更有效，而在刺激[3H]IP4受体结合方面，Pb（IC50 30 microM）比MM（IC50 133 microM）更有效。当大鼠腹腔注射Hg（5 mg/kg体重）或MM（5 mg/kg体重）或Pb（25 mg/kg体重）3小时或24小时后，在海马体和大脑皮层中未观察到[3H]IP3受体结合的显著变化。但是，上述对大鼠进行3小时或24小时的Pb或MM处理导致大脑皮层膜中[3H]IP4受体结合增加。然而，用Hg（1 mg/kg体重/天）或Pb（25 mg/kg体重/天）处理大鼠7天，未显示海马体膜中[3H]IP3与其受体的结合有任何变化，但用MM（2.5 mg/kg体重/天）处理7天则观察到这种受体结合增加。上述用MM或Pb处理7天的大鼠的海马体和大脑皮层中[3H]IP4受体结合增加。这些体外和体内数据表明，金属对肌醇多磷酸受体结合的改变可能导致细胞内钙水平的改变，这可能影响神经元活动。
