Hay D W, Muccitelli R M, Horstemeyer D L, Raeburn D
Smith Kline & French Laboratories, Department of Pharmacology, King of Prussia, PA 19406-0939.
Prostaglandins. 1988 Apr;35(4):625-37. doi: 10.1016/0090-6980(88)90036-6.
To examine further the possible prostanoid involvement in the influence of the epithelium on guinea-pig tracheal smooth muscle responsiveness, we have analyzed the effects of LTD4, methacholine and histamine on the level of airway smooth muscle tone and on the amounts of PGE2, PGF2 alpha and PGI2 (determined by radioimmunoassay) in the presence and absence of the epithelium. Removal of the epithelium increased the sensitivity of guinea-pig trachea to the contractile effects of LTD4, methacholine and histamine. LTD4 (3-100 nM), methacholine (0.1-10 microM) or histamine (0.3-30 microM) did not increase prostanoid release above control values in either the presence or absence of the epithelium. The unstimulated release of PGE2 and PGF2 alpha, but not PGI2, was decreased in tissues lacking epithelium. Indomethacin (1 microM) reduced the baseline tone to a smaller extent in the absence of epithelium. In the presence but not the absence of the epithelium, indomethacin increased the sensitivity of preparations to the contractile effect of methacholine. The results support the postulate of an epithelium-derived inhibitory factor modulating guinea-pig tracheal smooth muscle responsiveness. The identity of this factor is not known but is not PGI2 and is unlikely to be PGF2 alpha or PGE2. However, the possibility remains that the basal release of PGE2 and/or PGF2 alpha derived from the epithelium may markedly affect the responsiveness of guinea-pig tracheal smooth muscle. Furthermore, the epithelium is a significant source of PGE2 and PGF2 alpha which may be involved in the maintenance of baseline tone.
为了进一步研究前列腺素类物质是否参与上皮对豚鼠气管平滑肌反应性的影响，我们分析了在有上皮和无上皮存在的情况下，白三烯D4（LTD4）、乙酰甲胆碱和组胺对气道平滑肌张力水平以及前列腺素E2（PGE2）、前列腺素F2α（PGF2α）和前列环素（PGI2）含量（通过放射免疫分析法测定）的影响。去除上皮会增加豚鼠气管对LTD4、乙酰甲胆碱和组胺收缩作用的敏感性。无论有无上皮存在，LTD4（3 - 100 nM）、乙酰甲胆碱（0.1 - 10 μM）或组胺（0.3 - 30 μM）均不会使前列腺素类物质的释放量高于对照值。在缺乏上皮的组织中，PGE2和PGF2α（而非PGI2）的基础释放量减少。吲哚美辛（1 μM）在无上皮存在时对基线张力的降低作用较小。在有上皮存在但无上皮不存在时，吲哚美辛会增加标本对乙酰甲胆碱收缩作用的敏感性。这些结果支持了一种由上皮衍生的抑制因子调节豚鼠气管平滑肌反应性的假设。该因子的身份尚不清楚，但不是PGI2，也不太可能是PGF2α或PGE2。然而，上皮来源的PGE2和/或PGF2α的基础释放仍有可能显著影响豚鼠气管平滑肌的反应性。此外，上皮是PGE2和PGF2α的重要来源，它们可能参与基线张力的维持。
