Kato Eisuke, Kimura Shunsuke, Kawabata Jun
Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan.
Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan.
Bioorg Med Chem. 2017 Dec 15;25(24):6412-6416. doi: 10.1016/j.bmc.2017.10.011. Epub 2017 Oct 14.
β2-Adrenergic receptor (β2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has β2AR agonist activity, but the involvement of each functional groups in β2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through β2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 4'-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer.
β2-肾上腺素能受体（β2AR）激动剂被用作支气管扩张剂来治疗肺部疾病，但它们对葡萄糖代谢和能量消耗的调节作用正引起人们的关注。去甲乌药碱是存在于多种植物中的一种四氢异喹啉，具有β2AR激动剂活性，但很少有人研究其各个官能团在β2AR激动剂活性中的作用以及与内源性儿茶酚胺（多巴胺、肾上腺素和去甲肾上腺素）相比的有效性。已知肌肉细胞的葡萄糖摄取是通过β2AR激活来诱导的。在此比较了去甲乌药碱与去甲乌药碱的几种甲基化衍生物或内源性儿茶酚胺增强葡萄糖摄取的能力。我们发现：（i）去甲乌药碱除4'-羟基外的官能团是增强葡萄糖摄取所必需的；（ii）去甲乌药碱增强葡萄糖摄取的能力与肾上腺素和去甲肾上腺素相当；（iii）S-异构体增强葡萄糖摄取的能力比R-异构体更强。
