Reid J J, Stitzel R E, Head R J
J Pharm Pharmacol. 1986 Jan;38(1):46-50. doi: 10.1111/j.2042-7158.1986.tb04465.x.
The effect of in-vitro sympathetic denervation on the O-methylation of 2-hydroxyoestradiol was examined using the rabbit thoracic aorta. Aortic segments were exposed to 6-hydroxydopamine (400 mg litre-1, 10 min), incubated in 2-hydroxyoestradiol (5 microM, 60 min), and the 2-methoxyoestradiol formed was quantified using HPLC with electrochemical detection. Pre-exposure to 6-hydroxydopamine reduced O-methylation by 90% in intact aortic strips. However, O-methylation was also reduced (81%) in rabbit aorta that had been surgically denervated before exposure to 6-hydroxydopamine. Furthermore, the O-methylation of 2-hydroxyoestradiol (20 microM, 15 min) by partially purified soluble catechol-O-methyltransferase was inhibited by 6-hydroxydopamine (400 mg litre-1) by 95% and 51% in the absence and presence of antioxidant, respectively. These results suggest that the inhibition of catechol-O-methyltransferase by 6-hydroxydopamine reported for the purified enzyme, applies to the intact tissue and that the inhibition is dependent on oxidation of the 6-hydroxydopamine. Subsequent experiments using dialysis techniques demonstrated that the inhibition of soluble catechol-O-methyltransferase by 6-hydroxydopamine was irreversible in part, but the degree of irreversibility was influenced by pH and by the extent of in-vitro oxidation of 6-hydroxydopamine.
利用兔胸主动脉研究了体外交感神经去神经支配对2-羟基雌二醇O-甲基化的影响。将主动脉段暴露于6-羟基多巴胺（400mg/L，10分钟），在2-羟基雌二醇（5μM，60分钟）中孵育，并用高效液相色谱-电化学检测法定量形成的2-甲氧基雌二醇。预先暴露于6-羟基多巴胺可使完整主动脉条中的O-甲基化减少90%。然而，在暴露于6-羟基多巴胺之前已手术去神经的兔主动脉中，O-甲基化也减少了（81%）。此外，在不存在和存在抗氧化剂的情况下，6-羟基多巴胺（400mg/L）分别抑制部分纯化的可溶性儿茶酚-O-甲基转移酶对2-羟基雌二醇（20μM，15分钟）的O-甲基化95%和51%。这些结果表明，已报道的纯化酶中6-羟基多巴胺对儿茶酚-O-甲基转移酶的抑制作用也适用于完整组织，且该抑制作用取决于6-羟基多巴胺的氧化。随后使用透析技术进行的实验表明，6-羟基多巴胺对可溶性儿茶酚-O-甲基转移酶的抑制作用部分是不可逆的，但不可逆程度受pH值和6-羟基多巴胺体外氧化程度的影响。
