Vinge E, Andersson K E, Persson C G
Acta Physiol Scand. 1984 Jan;120(1):117-21. doi: 10.1111/j.1748-1716.1984.tb07380.x.
Adenosine receptor antagonism has been suggested to be the cellular basis for many extrapulmonary actions of xanthine derivatives, such as theophylline. Enprofylline (3-propylxanthine) is a poor adenosine antagonist but is five times as potent as theophylline as a bronchodilator in man. Adenosine is a potent inhibitor of platelet aggregation, but also xanthines are considered to exert this action. In the present study, effects of theophylline and enprofylline on ADP-induced aggregation of human platelets were studied in vitro. Theophylline alone in concentrations exceeding 280 microM inhibited platelet aggregation concentration-dependently. Enprofylline alone mimicked this effect but was about five times more potent than theophylline. At the lowest concentrations used, corresponding to upper therapeutic levels, neither of the two xanthines affected platelet aggregation by ADP. The interactions between these low concentrations of the xanthines and adenosine were then evaluated. In the presence of theophylline 110 microM the inhibitory effect of adenosine 4 microM was attenuated, whereas the presence of enprofylline 21 microM enforced the inhibitory effect of adenosine. Thus, at low concentrations where neither theophylline nor enprofylline inhibits platelet aggregation theophylline antagonizes the antiaggregatory effect of adenosine, whereas enprofylline acts in synergy with this nucleoside.
腺苷受体拮抗作用被认为是黄嘌呤衍生物（如茶碱）许多肺外作用的细胞基础。恩丙茶碱（3 - 丙基黄嘌呤）是一种较弱的腺苷拮抗剂，但在人体中作为支气管扩张剂的效力是茶碱的五倍。腺苷是血小板聚集的强效抑制剂，但黄嘌呤也被认为具有这种作用。在本研究中，体外研究了茶碱和恩丙茶碱对ADP诱导的人血小板聚集的影响。单独使用浓度超过280微摩尔的茶碱可浓度依赖性地抑制血小板聚集。单独使用恩丙茶碱可模拟这种效应，但效力约为茶碱的五倍。在使用的最低浓度下，相当于治疗上限水平，两种黄嘌呤均未影响ADP诱导的血小板聚集。然后评估了这些低浓度黄嘌呤与腺苷之间的相互作用。在存在110微摩尔茶碱的情况下，4微摩尔腺苷的抑制作用减弱，而存在21微摩尔恩丙茶碱则增强了腺苷的抑制作用。因此，在茶碱和恩丙茶碱均不抑制血小板聚集的低浓度下，茶碱拮抗腺苷的抗聚集作用，而恩丙茶碱则与这种核苷协同作用。
