Shimura S, Ishihara H, Satoh M, Masuda T, Nagaki N, Sasaki H, Takishima T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Am J Physiol. 1992 Feb;262(2 Pt 1):L208-13. doi: 10.1152/ajplung.1992.262.2.L208.
We examined the effects of endothelin on both the trichloroacetic acid precipitable 3H-labeled glycoconjugate release and intracellular Ca2+ concentration ([Ca2+]i]) measured by the usage of fura-2 in submucosal glands isolated from feline trachea. Endothelin-1 produced a significant increase in glycoconjugate release from the isolated glands in a dose-dependent fashion, reaching a response of 161% of the control at 10(-6) M. Atropine, propranolol, phentolamine, or indomethacin did not produce any significant alterations in the ET-1-evoked glycoconjugate secretion from the isolated glands. In contrast, in tracheal explants which contained epithelium, ET-1 produced a significant reduction in the glycoconjugate secretion in a dose-dependent fashion, reaching a response of 59% of the control at 10(-6) M. In the presence of cultured epithelial cells, ET-1 also produced a significant reduction in the glycoconjugate secretion from isolated glands. In isolated glands, ET-1 produced a sustained increase in the [Ca2+]i which was abolished by the removal of Ca2+ from the medium or by the presence of cultured epithelial cells. Pretreatment with indomethacin failed to alter the epithelial inhibitory action evoked by ET-1 in both the glycoconjugate secretion and the [Ca2+]i in isolated glands. ET-2 and ET-3 failed to produce significant alterations in the glycoconjugate secretion or [Ca2+]i. These findings indicate 1) that ET-1 induces mucus glycoprotein secretion via a Ca2+ influx and 2) that it possibly augments the an epithelial action inhibitory to the mucus glycoprotein secretion from airway submucosal glands.
我们研究了内皮素对从猫气管分离的黏膜下腺中三氯乙酸可沉淀的3H标记糖缀合物释放以及通过使用fura-2测量的细胞内Ca2+浓度（[Ca2+]i）的影响。内皮素-1以剂量依赖性方式使分离腺体中的糖缀合物释放显著增加，在10(-6) M时达到对照的161%的反应。阿托品、普萘洛尔、酚妥拉明或吲哚美辛对ET-1诱发的分离腺体中糖缀合物分泌没有产生任何显著改变。相反，在含有上皮的气管外植体中，ET-1以剂量依赖性方式使糖缀合物分泌显著减少，在10(-6) M时达到对照的59%的反应。在存在培养的上皮细胞时，ET-1也使分离腺体中的糖缀合物分泌显著减少。在分离腺体中，ET-1使[Ca2+]i持续增加，这可通过从培养基中去除Ca2+或存在培养的上皮细胞而消除。用吲哚美辛预处理未能改变ET-1在分离腺体中糖缀合物分泌和[Ca2+]i方面诱发的上皮抑制作用。ET-2和ET-3在糖缀合物分泌或[Ca2+]i方面未能产生显著改变。这些发现表明：1）ET-1通过Ca2+内流诱导黏液糖蛋白分泌；2）它可能增强对气道黏膜下腺黏液糖蛋白分泌的上皮抑制作用。
