Knight D A, Phillips M J, Stewart G A, Thompson P J
University Dept of Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia.
Eur Respir J. 1991 Sep;4(8):985-91.
The interaction of histamine (Hist) and acetylcholine (ACh) on human isolated bronchial smooth muscle (HIBSM) contraction, and the influence of the epithelium, was assessed using HIBSM obtained from 15 patients undergoing thoracotomy. Cumulative concentration effect curves for ACh and Hist, together with combinations of equipotent concentrations of both agonists, were generated using both epithelium-intact and epithelium-denuded HIBSM. In epithelium-denuded HIBSM both ACh (p less than 0.05) and Hist (p less than 0.005) produced a significantly enhanced maximal response and a 2.1 fold increase in the potency of ACh (p less than 0.02, n = 13). When ACh and Hist were added simultaneously, in equipotent concentrations, to epithelium-intact HIBSM, a significantly less (p less than 0.0005, n = 13) than additive response occurred with only 60% of the predicted maximum response being observed. However, following epithelium removal, an additive interaction between the two agonists (n = 8) occurred. Using HIBSM from five of the original 15 patients, similar experiments were performed to determine the influence of the muscarinic receptor antagonist atropine (0.1 microM) and the H1 receptor antagonist mepyramine (10 microM). Both resulted in a significantly less than additive interaction (40-50% of predicted tensions). Similar experiments were also performed in the presence of the cyclo-oxygenase inhibitor indomethacin (5 microM) and these failed to reverse the inhibition observed in HIBSM contraction (n = 5). The inhibitory interaction between ACh and Hist appears to be epithelium dependent and is not mediated via the release of prostanoids. Thus, there appears to be a complex interaction between contractile agonists and the epithelium, which is not just a simple summation of the activation of individual receptors on HIBSM.
利用从15例开胸手术患者获取的人离体支气管平滑肌（HIBSM），评估组胺（Hist）和乙酰胆碱（ACh）对其收缩的相互作用以及上皮的影响。使用完整上皮和去上皮的HIBSM生成ACh和Hist的累积浓度效应曲线，以及两种激动剂等效浓度的组合。在去上皮的HIBSM中，ACh（p<0.05）和Hist（p<0.005）均产生显著增强的最大反应，ACh的效价增加2.1倍（p<0.02，n = 13）。当将等效浓度的ACh和Hist同时添加到完整上皮的HIBSM中时，出现明显小于相加的反应（p<0.0005，n = 13），仅观察到预测最大反应的60%。然而，去除上皮后，两种激动剂之间出现相加相互作用（n = 8）。使用最初15例患者中5例患者的HIBSM进行类似实验，以确定毒蕈碱受体拮抗剂阿托品（0.1μM）和H1受体拮抗剂美吡拉敏（10μM）的影响。两者均导致明显小于相加的相互作用（预测张力的40 - 50%）。在环氧化酶抑制剂吲哚美辛（5μM）存在的情况下也进行了类似实验，这些实验未能逆转在HIBSM收缩中观察到的抑制作用（n = 5）。ACh和Hist之间的抑制性相互作用似乎依赖于上皮，且不是通过前列腺素的释放介导的。因此，收缩性激动剂与上皮之间似乎存在复杂的相互作用，这不仅仅是HIBSM上各个受体激活的简单相加。
