Fedan J S, Nutt M E, Frazer D G
Physiology Section, National Institute for Occupational Safety and Health, Morgantown, WV 26505.
Eur J Pharmacol. 1990 Nov 13;190(3):337-45. doi: 10.1016/0014-2999(90)94198-7.
Guinea-pig tracheas were perfused with recirculating modified Krebs-Henseleit solution while monitoring changes in inflow-outflow pressure difference, which is an index of trachealis muscle tone. The reactivities of the trachealis muscle to methacholine, histamine and isoproterenol applied separately to the mucosal (intraluminal, IL) or serosal (extraluminal, EL) compartments were compared, and evidence for the agonist-induced release of epithelium-derived relaxing factor (EpDRF) was sought. All agents were more potent when added to the EL compartment, but the IL/EL EC50 ratios were different: 100 for methacholine, 41 for histamine and 25 for isoproterenol. Methacholine or histamine added to the IL compartment, after the preparations were pre-contracted with the same concentration of the agonist or 30 mM KCl added EL, did not result in relaxation. Likewise, IL isoproterenol did not evoke contraction. IL KCl evoked relaxation. The results indicate that the epithelium reduces access of bronchoactive agents to the muscle, while an immediate relaxant effect of EpDRF released by agonists could not be demonstrated.
在用循环的改良Krebs-Henseleit溶液灌注豚鼠气管的同时,监测流入-流出压力差的变化,该压力差是气管平滑肌张力的一个指标。比较了气管平滑肌分别对施加于黏膜(管腔内,IL)或浆膜(管腔外,EL)腔室的乙酰甲胆碱、组胺和异丙肾上腺素的反应性,并寻找激动剂诱导的上皮衍生舒张因子(EpDRF)释放的证据。当添加到EL腔室时,所有药物的效力更强,但IL/EL的半数有效浓度(EC50)比值不同:乙酰甲胆碱为100,组胺为41,异丙肾上腺素为25。在制剂用相同浓度的激动剂或添加到EL的30 mM氯化钾预收缩后,添加到IL腔室的乙酰甲胆碱或组胺并未导致舒张。同样,IL异丙肾上腺素也未引起收缩。IL氯化钾引起舒张。结果表明,上皮减少了支气管活性剂与肌肉的接触,而激动剂释放的EpDRF的即时舒张作用未能得到证实。