除草剂乙草胺抑制大鼠肝脏细胞肾上腺素能受体所介导的胞浆钙振荡（英文）

田间除草剂乙草胺施用之后非常容易进入地表水和地下水，河流溪水中乙草胺浓度可达纳摩尔水平，从而对水生生物产生长期影响.因职业关系而产生的皮肤暴露和吸入，可导致人血液乙草胺浓度达到微摩尔水平.对乙草胺体内动力学的研究，发现肝脏是乙草胺毒理作用的主要靶器官.已知在肝脏细胞多种生理功能中，钙离子发挥重要作用.本文研究在新鲜分离的大鼠肝脏细胞，乙草胺对肾上腺素能受体所介导胞浆钙振荡的可能影响.实验发现低浓度乙草胺(1、10μmol·L^-1)对苯丙肾上腺素所诱导钙振荡没有影响，但是高浓度(50、100、200μmol·L^-1)乙草胺在有些肝脏细胞可逆性抑制苯丙肾上腺素所诱导的胞浆钙振荡.在苯丙肾上腺素2次串联刺激之间短暂加入乙草胺(1、10、100μmol·L^-1)，乙草胺对肝脏细胞基础钙浓度没有影响，也不影响第2次苯丙肾上腺素刺激所引发胞浆钙振荡.细胞免疫化学研究发现在新鲜分离的大鼠肝脏不同细胞，α1肾上腺素能受体密度存在明显差异.对固定的大鼠肝脏切片进行组织免疫化学检测，发现α1肾上腺素能受体在肝脏小叶的密度梯度分布：α1肾上腺...

Herbicide acetochlor inhibits adrenergic receptor-mediated calcium oscillations in rat hepatocytes

Herbicide acetochlor after application enters both surface and underground waters, so that acetochlor concentrations in rivers and streams could be sufficiently high (nmol·L?1) to exert long-term effects in aquatic animals．Occupational exposure may pose greater risks due to skin and inhalation exposures, resulting in much higher transient blood acetochlor concentrations (μmol·L?1)．Previous works have identified liver as the most susceptible toxicological target for acetochlor, and cytosolic calcium is known to play a vital role in multiple hepatocyte functions．Therefore the present work aims to examine acetochlor effect on calcium oscillations induced by adrenergic receptor activation in freshly isolated rat hepatocytes. It was found that acetochlor at lower concentrations (1, 10 μmol·L?1) added simultaneously with phenylepinephrine (PE) had no effect on PE-induced calcium oscillations, but inhibited reversibly calcium oscillations at higher doses (50, 100, 200 μmol·L?1) of acetochlor in selected hepatocytes．Brief prior acetochlor exposure (1, 10, 100 μmol·L?1), however, had no apparent effect on either basal calcium or subsequent PE-induced calcium oscillations．Immunocytochemistry identified non-uniform α1 adrenergic receptor expression among isolated hepatocytes．Immunohistochemistry of liver slices revealed a distinct pattern of α1 adrenergic receptor density in liver lobules: a gradual low-to-high receptor density gradient from pericentral to periportal regions．This receptor density gradient is likely related to acetochlor inhibition in selected hepatocytes．Taken together it is concluded that acetochlor at blood concentrations attainable during acute skin exposure or acetochlor poisoning may exert transient inhibitory effects on α1 receptor signaling in the liver．