Knight D A, Stewart G A, Thompson P J
Asthma and Allergy Research Unit, University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia.
Eur J Pharmacol. 1995 Jan 5;272(1):13-9. doi: 10.1016/0014-2999(94)00602-4.
The effects of exogenous prostaglandin E2 and prostacyclin on the function of epithelium-intact and epithelium-denuded human bronchial smooth muscle and the role of these mediators in the inhibition of histamine-induced contraction was examined using bronchi obtained from 22 patients undergoing thoracotomy. Under resting tension, a variable biphasic contraction-relaxation or monophasic relaxation was observed following the cumulative addition of exogenous prostaglandin E2 or prostacyclin. Cumulative addition of these mediators to pre-contracted bronchi produced incomplete relaxation, irrespective of the presence of epithelium. Addition of prostaglandin E2, at a concentration equating to that produced after histamine stimulation (1.2 x 10(-9)M), produced a reduction (24%) in the maximum contractile response (Emax) to a subsequent histamine challenge (P < 0.03). However, a similar response was not observed after the addition of prostacyclin at a concentration similar to that produced endogenously (6.5 x 10(-10)M). The combined addition of both mediators resulted in a significant reduction (26%) in the Emax to histamine (P < 0.02) but this effect was not statistically different to that of prostaglandin E2 alone. The addition of supramaximal concentrations (1 microM) of each prostanoid, either alone or in combination, did not inhibit responses to histamine. These data suggest that whilst prostaglandin E2 does not act as a direct acting relaxant agonist, it may inhibit histamine-induced muscle contraction and thereby contribute to the observed tachyphylaxis to this mediator. In contrast, prostacyclin appears to be of little importance in modulating human bronchial smooth muscle responses to histamine either directly or by enhancing responses to prostaglandin E2. The inhibitory effect of prostaglandin E2 appears to be concentration-dependent and suggests a bimodal action of this mediator in human airways.
利用22例开胸手术患者的支气管，研究了外源性前列腺素E2和前列环素对上皮完整和上皮剥脱的人支气管平滑肌功能的影响，以及这些介质在抑制组胺诱导的收缩中的作用。在静息张力下，累积添加外源性前列腺素E2或前列环素后，观察到可变的双相收缩 - 舒张或单相舒张。无论上皮是否存在，将这些介质累积添加到预收缩的支气管中均产生不完全舒张。添加与组胺刺激后产生的浓度相当的前列腺素E2（1.2×10⁻⁹M），可使对随后组胺激发的最大收缩反应（Emax）降低（24%）（P < 0.03）。然而，添加与内源性产生的浓度相似的前列环素（6.5×10⁻¹⁰M）后未观察到类似反应。两种介质联合添加导致对组胺的Emax显著降低（26%）（P < 0.02），但该效应与单独使用前列腺素E2的效应在统计学上无差异。添加每种前列腺素的超最大浓度（1μM），单独或联合使用，均不抑制对组胺的反应。这些数据表明，虽然前列腺素E2不作为直接作用的舒张激动剂，但它可能抑制组胺诱导的肌肉收缩，从而导致对该介质的快速减敏。相比之下，前列环素似乎在直接调节人支气管平滑肌对组胺的反应或通过增强对前列腺素E2的反应方面作用不大。前列腺素E2的抑制作用似乎是浓度依赖性的，提示该介质在人气道中具有双峰作用。
