Bailey C, Kitchen I
Brain Res. 1985 Sep;354(1):75-9. doi: 10.1016/0165-3806(85)90070-7.
Certain developmental abnormalities have been associated with environmental exposure to lead and our previous studies have indicated that the endogenous opioid system is disrupted by this metal. In connection with this we report the ontogeny of proenkephalin products in the rat striatum determined by combined HPLC and bioassay and the effects of low-level lead exposure on this ontogeny. The development of Met-enkephalin levels was dissimilar from that of the other proenkephalin products, Met-enkephalyl-Arg6-Phe7, Met-enkephalyl-Arg6-Gly7-Leu8 and Leu-enkephalin. The ratios of Met-enkephalin containing peptides to Leu-enkephalin was less than the 6:1 ratio predicted from the proenkephalin structure. Lead (administered in the maternal drinking water, from conception to weaning at 100, 300 and 1000 ppm) caused a dose-related depression of the levels of proenkephalin products in rat striatum at 10, 21 and 30 days after birth. The most pronounced effects were observed at 10 days and the most persistent effects were seen with Met-enkephalin. Peak blood lead levels were below 45 micrograms/100 ml in the 100 and 300 ppm lead-dosed groups and in all lead-dosed groups at 10 days after birth. It is suggested that lead may have inhibitory effects on proenkephalin-processing enzymes.
某些发育异常与环境铅暴露有关，我们之前的研究表明内源性阿片系统会被这种金属破坏。与此相关，我们报告了通过高效液相色谱法和生物测定法联合测定的大鼠纹状体中前脑啡肽产物的个体发生情况，以及低水平铅暴露对这种个体发生的影响。甲硫氨酸脑啡肽水平的发育与其他前脑啡肽产物，即甲硫氨酸脑啡肽-精氨酸6-苯丙氨酸7、甲硫氨酸脑啡肽-精氨酸6-甘氨酸7-亮氨酸8和亮氨酸脑啡肽不同。含甲硫氨酸脑啡肽的肽与亮氨酸脑啡肽的比例低于从前脑啡肽结构预测的6:1比例。铅（在母鼠饮用水中给药，从受孕到断奶，剂量为100、300和1000 ppm）在出生后10天、21天和30天导致大鼠纹状体中前脑啡肽产物水平出现剂量相关的降低。在10天时观察到最明显的影响，对甲硫氨酸脑啡肽的影响最为持久。在100和300 ppm铅剂量组以及所有铅剂量组出生后10天时，血铅峰值水平低于45微克/100毫升。提示铅可能对前脑啡肽加工酶有抑制作用。
