CALCIUM CHANNEL BLOCKADE BY METHYLMETHACRYLATE

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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.