Slotkin T A, Kavlock R J, Cowdery T, Orband L, Bartolome M, Whitmore W L, Bartolome J
Toxicology. 1986 Oct;41(1):95-106. doi: 10.1016/0300-483x(86)90107-1.
Neonatal exposure to methylmercury produces changes in patterns of tissue growth and function, in part, due to alterations in adrenergic neuronal input. To explore the mechanisms by which these changes come about, newborn rats were exposed to methylmercury (1 or 2.5 mg/kg per day) throughout the preweaning stage and the ontogeny of adrenergic receptor binding sites evaluated in liver, kidney, heart and lung, using [3H]prazosin (alpha 1-receptors), [3H]rauwolscine (alpha 2-receptors) and [125I]pindolol (beta-receptors). In the kidney, methylmercury caused decreases in beta- and alpha 1-receptor binding and increases in alpha 2-binding; previous work has shown that beta-receptor-mediated responses are generally enhanced in methylmercury-exposed pups, and the down-regulation of beta-receptor binding thus probably represents a compensatory action secondary to alterations in post-receptor coupling mechanisms. The effects of methylmercury on hepatic adrenergic receptors were different from those seen in the kidney, with substantial elevations in beta- and alpha 1-receptor binding apparent in the preweaning stage; this agrees also with the differences in effects of the mercurial on trophic reactivity and growth in the 2 tissues. Despite the fact that methylmercury causes activation of neonatal cardiac sympathetic nerves, beta-receptor binding sites in the heart were unaffected by methylmercury exposure; the failure to down-regulate cardiac postsynaptic receptors in the face of increased nerve activity again represents an anomaly of synaptic regulatory function. These results indicate that methylmercury alters adrenergic responsiveness, in part, through actions on the development of receptor binding sites, and further, that the organ-specificity and receptor subtype-selectivity are consistent with subsequent effects of the organomercurial on adrenergic participation in target organ growth; however, changes in receptor binding alone do not account for all of the effects of methylmercury on synaptic activity or trophic responses.
新生儿接触甲基汞会导致组织生长和功能模式发生变化，部分原因是肾上腺素能神经元输入的改变。为了探究这些变化产生的机制，在断奶前阶段，新生大鼠每天暴露于甲基汞（1或2.5毫克/千克），并使用[3H]哌唑嗪（α1受体）、[3H]育亨宾（α2受体）和[125I]吲哚洛尔（β受体）评估肝脏、肾脏、心脏和肺中肾上腺素能受体结合位点的个体发生情况。在肾脏中，甲基汞导致β受体和α1受体结合减少，α2受体结合增加；先前的研究表明，在接触甲基汞的幼崽中，β受体介导的反应通常会增强，因此β受体结合的下调可能代表受体后偶联机制改变后的一种代偿作用。甲基汞对肝脏肾上腺素能受体的影响与在肾脏中观察到的不同，在断奶前阶段，β受体和α1受体结合明显大幅升高；这也与汞对这两种组织的营养反应性和生长的影响差异一致。尽管甲基汞会激活新生儿心脏交感神经，但心脏中的β受体结合位点不受甲基汞暴露的影响；面对增加的神经活动，未能下调心脏突触后受体再次代表了突触调节功能的异常。这些结果表明，甲基汞部分通过作用于受体结合位点的发育来改变肾上腺素能反应性，此外，器官特异性和受体亚型选择性与有机汞对肾上腺素能参与靶器官生长的后续影响一致；然而，仅受体结合的变化并不能解释甲基汞对突触活动或营养反应的所有影响。
