de Paulis Tomas, Schmidt Dennis E, Bruchey Aleksandra K, Kirby Michael T, McDonald Michael P, Commers Patricia, Lovinger David M, Martin Peter R
Institute for Coffee Studies, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Eur J Pharmacol. 2002 May 10;442(3):215-23. doi: 10.1016/s0014-2999(02)01540-6.
Preliminary screening of a minor, non-xanthine constituent of roasted coffee, 3,4-diferuloyl-1,5-quinolactone (DIFEQ), showed inhibition of the adenosine transporter at low micromolar concentration. DIFEQ is a neutral derivative of the chlorogenic acids, i.e. isomeric mono- and di-substituted coumaroyl-, caffeoyl-, and feruloyl-esters of quinic acid, formed in the roasting process of coffee. Displacement of the adenosine transporter antagonist (3)H-(nitrobenzyl)-6-thioinosine binding by DIFEQ in cultured U-937 cell preparations, expressing the human adenosine transporter protein (hENT1), showed a K(i) of 0.96+/-0.13 microM. Extracts of regular and decaffeinated coffee showed binding activities equivalent to 30-40 mg DIFEQ per three cups of coffee. Acute administration of a high dose of DIFEQ (100 mg/kg i.p.) reduced open field locomotion in mice for 20 min in correlation with brain levels of DIFEQ. Both 3,4-dicaffeoyl-1,5-quinide and 3,4-dicoumaroyl-1,5-quinide, two close structural analogs of DIFEQ also present in roasted coffee, showed similar affinities for the adenosine transporter, while the corresponding 3- and 4-mono caffeoyl- and feruloyl-quinides were one to two orders of magnitudes less active. This suggests that 3,4-dicinnamoyl-1,5-quinides in coffee could have the potential to raise extra-cellular adenosine levels, thereby counteracting the stimulant effect of caffeine.
对烘焙咖啡中的一种微量非黄嘌呤成分3,4 - 二阿魏酰基 - 1,5 - 奎尼内酯（DIFEQ）进行的初步筛选表明，它在低微摩尔浓度下可抑制腺苷转运体。DIFEQ是绿原酸的中性衍生物，即奎尼酸的异构单取代和二取代香豆酰基、咖啡酰基和阿魏酰基酯，在咖啡烘焙过程中形成。在表达人腺苷转运蛋白（hENT1）的培养U - 937细胞制剂中，DIFEQ对腺苷转运体拮抗剂(3)H-(硝基苄基)-6 - 硫代肌苷结合的置换显示其抑制常数（K(i)）为0.96±0.13微摩尔。常规咖啡和脱咖啡因咖啡的提取物显示出的结合活性相当于每三杯咖啡含有30 - 40毫克DIFEQ。急性给予高剂量的DIFEQ（100毫克/千克腹腔注射）可使小鼠的旷场运动减少20分钟，这与脑中DIFEQ的水平相关。烘焙咖啡中也存在的DIFEQ的两种紧密结构类似物3,4 - 二咖啡酰基 - 1,5 - 奎尼德和3,4 - 二香豆酰基 - 1,5 - 奎尼德对腺苷转运体显示出相似的亲和力，而相应的3 - 和4 - 单咖啡酰基和阿魏酰基奎尼德的活性则低一到两个数量级。这表明咖啡中的3,4 - 二肉桂酰基 - 1,5 - 奎尼德可能有提高细胞外腺苷水平的潜力，从而抵消咖啡因的刺激作用。
