CALCIUM CHANNEL BLOCKADE BY METHYLMETHACRYLATE

甲基丙烯酸甲酯（MMA）和其他甲基丙烯酸酯 (MAA)非常普遍地用于工业、商业和 医疗设置，如塑料、油漆、地板饰面、外科骨 胶合剂和接触透镜。 我们的初步研究表明， 环境暴露于市售MMA聚合物地板 完成阻断正常的正性变时性反应， 兴奋性激动剂异丙肾上腺素， MMA和MAA单体阻断了血管的收缩反应， 子宫对几种兴奋性激动剂，而不减少 对KCl去极化的收缩反应。 拟议的研究 将表征MMA和MAA对激动剂的影响- 大鼠离体子宫的收缩和KCl引起的收缩 以及大鼠离体右心房的自发收缩， 并开始评估这些机制， 单体产生组织效应。 由于几个不同的 兴奋性激动剂在子宫和心房中被阻断，这些 MMA和MAA的作用似乎不是受体特异性的， 似乎更有可能是由于阻止共同的元素， 对每种兴奋性激动剂的反应，即进入 细胞外钙进入细胞。 如果这是真的， 单体具有独特的特异性（当与其它单体相比时）。 钙进入阻断剂），因为它们优先阻断 激动剂诱导效应而非去极化诱导效应 方面的影响. 这些研究将阐明MMA和MAA的作用 并帮助识别与暴露于 MMA或其他MAA聚合物。

Methylmethacrylate (MMA) and other esters of methacrylic acid (MAA) are very commonly used in industrial, commercial and medical settings as plastics, paints, floor finishes, surgical bone cements and contact lens. Our preliminary studies show that environmental exposure to a commercial MMA polymer floor finish blocks the normal positive chronotropic response of the isolated rat atria to the excitatory agonist isoproterenol, and that MMA and MAA monomers block the contractile response of the uterus to several excitatory agonists without reducing the contractile response to KCl depolarization. The proposed studies will characterize the effects of MMA and MAA on agonist- induced and KCl-induced contractions of the rat isolated uterus and the spontaneous contractions of the rat isolated right atria, and begin an evaluation of the mechanism by which these monomers produce tissue effects. Since several different excitatory agonists are blocked in the uterus and atria, these effects of MMA and MAA appear not to be receptor-specific but appear to be more likely due to blocking the common element in the response to each of the excitatory agonists, that is, entry of extracellular calcium into the cell. If this is true, these monomers have a unique specificity (when compared to other calcium entry blocking agents) in that they preferentially block agonist-induced effects rather than depolarization-induced effects. These studies will clarify the effects of MMA and MAA and help identify any health risks associated with exposure to MMA or other MAA polymers in the environment.