Saumon G, Martet G
INSERM U82, Faculté Xavier Bichat, Paris, France.
Pflugers Arch. 2001 Jan;441(4):559-65. doi: 10.1007/s004240000457.
An intact alveolar epithelial barrier is thought to be important for alveolar liquid absorption. However, polycations increase alveolar permeability without affecting alveolar liquid absorption (Saumon et al., Am J Physiol 1995: 269:L185-L194). We have reconsidered this issue using polyamines. The polyamine spermine (10(-3) mol/l) produced a large (up to 20-fold), sustained increase in the permeability of the alveolar barrier to mannitol (PAMan) and in alveolar liquid absorption (Jw, twofold) in isolated rat lungs. These increases were inhibited by 5 x 10(-3) mol/l putrescine and 2 x 10(-3) mol/l spermidine. Because spermine is known to affect the phosphoinositide/Ca2+ signalling pathway, we evaluated the effects of thiol reagents known to interfere with this pathway in different ways. Thimerosal, a thiol reagent which sensitizes the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the spermine-induced increase in PA(Man) and, to a lesser extent, that of Jw. Mersalyl, a thiol reagent which blocks IP3-gated Ca2+ channels, enhanced spermine's effect, whereas N-ethylmaleimide, a non-specific thiol reagent, had no effect. These observations show that large increases in permeability may coexist with increases in Jw. They also suggest that the phosphoinositide/Ca2+ second messenger pathway is involved in modulating the tightness of the alveolar barrier and alveolar liquid absorption.
完整的肺泡上皮屏障被认为对肺泡液体吸收很重要。然而，聚阳离子可增加肺泡通透性，而不影响肺泡液体吸收（Saumon等人，《美国生理学杂志》1995年：269：L185-L194）。我们使用多胺重新审视了这个问题。在离体大鼠肺中，多胺精胺（10⁻³ mol/l）使肺泡屏障对甘露醇的通透性（PAMan）大幅（高达20倍）持续增加，并使肺泡液体吸收（Jw，增加两倍）。这些增加被5×10⁻³ mol/l的腐胺和2×10⁻³ mol/l的亚精胺抑制。由于已知精胺会影响磷酸肌醇/Ca²⁺信号通路，我们评估了已知以不同方式干扰该通路的硫醇试剂的作用。硫柳汞是一种使肌醇1,4,5-三磷酸（IP3）受体敏感的硫醇试剂，它抑制了精胺诱导的PAMan增加，并在较小程度上抑制了Jw的增加。汞撒利是一种阻断IP3门控Ca²⁺通道的硫醇试剂，它增强了精胺的作用，而N-乙基马来酰亚胺这种非特异性硫醇试剂则没有作用。这些观察结果表明，通透性的大幅增加可能与Jw的增加同时存在。它们还表明，磷酸肌醇/Ca²⁺第二信使通路参与调节肺泡屏障的紧密性和肺泡液体吸收。
