Daxun Z, Rafferty P, Richards R, Summerell S, Holgate S T
Immunopharmacology Group, Southampton General Hospital, England.
J Allergy Clin Immunol. 1989 Jan;83(1):152-8. doi: 10.1016/0091-6749(89)90490-9.
Adenosine-5'-monophosphate (AMP) is a bronchoconstrictor agonist in subjects with atopic and nonatopic asthma. In this study we have investigated the effect of repeated airway challenge with AMP in 10 atopic, subjects without asthma. At the first visit, subjects had repeated inhalation challenges with increasing doubling concentrations of AMP, and the provocation concentration required to reduce FEV1 by 20% of baseline was determined (PC20 AMP). When the FEV1 had returned to within 5% of the baseline, the AMP challenge test was repeated on a further one or two occasions. When the maximum concentration of AMP (400 mg/ml) failed to produce a PC20, a bronchial provocation test with histamine was performed and the PC20 was determined. On the second visit, the effect of three consecutive inhalation challenge tests with histamine on the airway response to this agonist was determined. On the third visit, the duration of induced refractoriness to AMP was assessed. With the first AMP challenge, all subjects demonstrated bronchoconstriction with a geometric mean (GM) PC20 of 332 mg/ml. With a second AMP challenge, five of the 10 subjects became refractory and failed to achieve a PC20. In the remaining five subjects, the GM PC20 increased from 110 to 583 mg/ml. With a third AMP challenge, these subjects also failed to achieve a PC20. The initial GM PC20 histamine for the group was 22.9 mg/ml, which did not change significantly with two further histamine challenges or when the airways were refractory to AMP, suggesting that loss of AMP effect was not related to loss of contractility of airway smooth muscle or down regulation of H1-histamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
5'-单磷酸腺苷（AMP）是特应性和非特应性哮喘患者的支气管收缩激动剂。在本研究中，我们调查了10名无哮喘的特应性受试者反复接受AMP气道激发试验的效果。在首次就诊时，受试者接受递增双倍浓度AMP的反复吸入激发试验，并确定使第一秒用力呼气容积（FEV1）降低至基线值的20%所需的激发浓度（PC20 AMP）。当FEV1恢复到基线值的5%以内时，再进行一到两次AMP激发试验。当AMP的最大浓度（400 mg/ml）未能产生PC20时，进行组胺支气管激发试验并确定PC20。在第二次就诊时，确定连续三次组胺吸入激发试验对该激动剂气道反应的影响。在第三次就诊时，评估诱导的对AMP不应性的持续时间。首次AMP激发试验时，所有受试者均出现支气管收缩，几何平均（GM）PC20为332 mg/ml。第二次AMP激发试验时，10名受试者中有5名出现不应性，未能达到PC20。其余5名受试者中，GM PC20从110 mg/ml增加到583 mg/ml。第三次AMP激发试验时，这些受试者也未能达到PC20。该组最初的GM组胺PC20为22.9 mg/ml，在另外两次组胺激发试验或气道对AMP不应性时，该值无显著变化，提示AMP效应的丧失与气道平滑肌收缩力的丧失或H1组胺受体的下调无关。（摘要截短于250字）
