气管平滑肌舒张由钾通道激活剂BRL 38227诱导，上皮对此有部分抑制作用。

Partial inhibition by epithelium of tracheal smooth muscle relaxation induced by the potassium channel activator, BRL 38227.

作者信息

Pavlovic D, Brione E, De Vernejoul D, Aubier M

机构信息

Laboratoire de Pathologie Expérimentale, Unité INSERM 226, Faculté Xavier Bichat, Paris, France.

出版信息

Br J Pharmacol. 1993 Sep;110(1):139-44. doi: 10.1111/j.1476-5381.1993.tb13783.x.

DOI:10.1111/j.1476-5381.1993.tb13783.x

PMID:8220874

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2176044/

Abstract

A method is described whereby either the serosal (Out) or epithelial (In) sides of rat isolated tracheae were selectively perfused. Perfusion with BRL 38227 (10(-8)-5 x 10(-6) M; In/Out) of preparations with intact epithelium (+ EP) precontracted with carbachol (10(-6) M; Out/In) produced complete relaxation. Perfusion with aminophylline (10(-5)-10(-3) M; In) of + EP preparations precontracted with carbachol (10(-6) M; Out) also produced complete relaxation. 2. In preparations precontracted with carbachol (10(-6) M) epithelium removal (- EP) increased the sensitivity to the relaxant effect of BRL 38227 (In), but not BRL 38227 (Out) [- log EC50, + EP/- EP; carbachol (In), BRL 38227 (Out): 6.76 +/- 0.11 vs 6.67 +/- 0.15; carbachol (Out), BRL 38227 (In): 5.93 +/- 0.06 vs 6.25 +/- 0.07]. Removal of the epithelium increased also the sensitivity to BRL 38227 (In) of preparations precontracted with a lower concentration (5 x 10(-7) M) of carbachol (Out). [- log EC50, + EP/- EP, carbachol (Out), BRL 38227 (In): 6.19 +/- 0.14 vs 6.58 +/- 0.17]. 3. Removal of the epithelium did not affect the sensitivity to BRL 38227 (In) of preparations precontracted with a higher concentration (5 x 10(-6) M) of carbachol (Out). 4. In both + EP and - EP preparations precontracted with carbachol (10(-6) M; Out), BRL 38227 (In) had a more potent relaxant effect than aminophylline (In) (EC50, BRL 38227 vs aminophylline, + EP/- EP: 5.93 +/- 0.06 vs 3.66 +/- 0.11/6.25 +/- 0.07 vs 3.77 +/- 0.11). 5. In preparations precontracted with carbachol (10-6 M; Out), removal of the epithelium did not affect the sensitivity to aminophylline (In) but increased the degree of precontraction (Tmax) following epithelial but not serosal stimulation with carbachol.6. We conclude that BRL 38227, a K+ channel activator, is a potent relaxant of rat tracheal smooth muscle precontracted with carbachol, and that the effect can be partially inhibited by the presence of an intact tracheal epithelium, whereas the relaxant effect of aminophylline is not.

摘要

本文描述了一种可对大鼠离体气管的浆膜面（外）或上皮面（内）进行选择性灌注的方法。用BRL 38227（10⁻⁸ - 5×10⁻⁶ M；内/外）灌注预先用卡巴胆碱（10⁻⁶ M；外/内）预收缩的具有完整上皮（+ EP）的制剂，可产生完全舒张。用氨茶碱（10⁻⁵ - 10⁻³ M；内）灌注预先用卡巴胆碱（10⁻⁶ M；外）预收缩的 + EP制剂，也可产生完全舒张。2. 在预先用卡巴胆碱（10⁻⁶ M）预收缩的制剂中，去除上皮（- EP）可增加对BRL 38227（内）舒张作用的敏感性，但对BRL 38227（外）则无影响[- log EC50，+ EP/- EP；卡巴胆碱（内），BRL 38227（外）：6.76 ± 0.11对6.67 ± 0.15；卡巴胆碱（外），BRL 38227（内）：5.93 ± 0.06对6.25 ± 0.07]。去除上皮也增加了预先用较低浓度（5×10⁻⁷ M）卡巴胆碱（外）预收缩的制剂对BRL 38227（内）的敏感性。[- log EC50，+ EP/- EP，卡巴胆碱（外），BRL 38227（内）：6.19 ± 0.14对6.58 ± 0.17]。3. 去除上皮不影响预先用较高浓度（5×10⁻⁶ M）卡巴胆碱（外）预收缩的制剂对BRL 38227（内）的敏感性。4. 在预先用卡巴胆碱（10⁻⁶ M；外）预收缩的 + EP和 - EP制剂中，BRL 38227（内）的舒张作用比氨茶碱（内）更强（EC50，BRL 38227对氨茶碱，+ EP/- EP：5.93 ± 0.06对3.66 ± 0.11/6.25 ± 0.07对3.77 ± 0.11）。5. 在预先用卡巴胆碱（10⁻⁶ M；外）预收缩的制剂中，去除上皮不影响对氨茶碱（内）的敏感性，但在用卡巴胆碱刺激上皮而非浆膜后，增加了预收缩程度（Tmax）。6. 我们得出结论，K⁺通道激活剂BRL 38227是一种对预先用卡巴胆碱预收缩的大鼠气管平滑肌有强效舒张作用的物质，且该作用可被完整的气管上皮部分抑制，而氨茶碱的舒张作用则不受影响。