Nakahari T, Marunaka Y
The Medical Research Council Group in Lung Development and Division of Respiratory Research, The Hospital for Sick Children Research Institute, The University of Toronto Faculty of Medicine, Toronto, Ontario, Canada M5G 1X8.
J Membr Biol. 1996 May;151(1):91-100. doi: 10.1007/s002329900060.
Cell-volume changes induced by terbutaline (a specific beta2-agonist) were studied morphometrically in rat fetal distal lung epithelium (FDLE) cells. Cell-volume changes qualitatively differed with the concentration of terbutaline. Terbutaline of 10(-10)-10(-8) M induced transient cell swelling. Terbutaline of 10(-7) M induced transient cell swelling followed by slow cell shrinkage. Terbutaline of 10(-6)-10(-5) M induced rapid cell shrinkage followed by slow cell shrinkage. Terbutaline of 10(-3) M induced transient cell shrinkage; then cell volume oscillated during stimulation. Benzamil of 10(-6) M suppressed the cell swelling induced by 10(-10)-10(-8) M terbutaline and quinine of 10(-3) M inhibited the cell shrinkage induced by 10(-6)-10(-5) M terbutaline. These results suggest that cell swelling would be induced by NaCl influx and the cell shrinkage is by KCl efflux. Dibutyryl cyclic AMP (DBcAMP) also induced similar cell-volume changes over a wide range of concentrations (10(-9)-10(-3) M): a low concentration induced transient cell swelling; a high concentration, rapid and slow cell shrinkage. Forskolin (10(-4) M), like terbutaline (10(-5) M), induced rapid cell shrinkage followed by slow cell shrinkage, and this decrease in the cell volume was enhanced by the presence of benzamil. On the other hand, cell shrinkage was induced by ionomycin (even low concentration; 3 x 10(-10) M ionomycin), and after that cell volume remained at a plateau level. Removal of extracellular Ca2+ abolished the cell swelling caused by terbutaline of 10(-10)-10(-8) M. With removal of extracellular Ca2+, the initial, rapid cell shrinkage induced by 10(-5) M terbutaline became transient, but we still detected slow cell shrinkage similar to that in the presence of extracellular Ca2+. Overall, at low concentrations (10(-10)-10(-8) M), terbutaline induced benzamil-sensitive cell swelling in FDLE cells, which was cAMP- and Ca2+-dependent; high concentrations (> or =10(-6)) induced quinine-sensitive rapid cell shrinkage, which was Ca2+-dependent; high concentrations (> or = 10(-7)) induced slow cell shrinkage, which was cAMP-dependent. These findings suggest that terbutaline regulates cell volume in FDLE cells by cytosolic cAMP and Ca2+ through activation of Na+ and K+ channels.
用形态计量学方法研究了特布他林（一种特异性β2-肾上腺素能激动剂）诱导的大鼠胎儿远端肺上皮（FDLE）细胞的细胞体积变化。细胞体积变化在性质上因特布他林浓度而异。10^(-10)-10^(-8)M的特布他林诱导短暂的细胞肿胀。10^(-7)M的特布他林诱导短暂的细胞肿胀，随后是缓慢的细胞收缩。10^(-6)-10^(-5)M的特布他林诱导快速的细胞收缩，随后是缓慢的细胞收缩。10^(-3)M的特布他林诱导短暂的细胞收缩；然后在刺激过程中细胞体积振荡。10^(-6)M的苯扎米尔抑制10^(-10)-10^(-8)M特布他林诱导的细胞肿胀，10^(-3)M的奎宁抑制10^(-6)-10^(-5)M特布他林诱导的细胞收缩。这些结果表明，细胞肿胀可能是由NaCl内流引起的，而细胞收缩是由KCl外流引起的。二丁酰环磷腺苷（DBcAMP）在很宽的浓度范围（10^(-9)-10^(-3)M）内也诱导了类似的细胞体积变化：低浓度诱导短暂的细胞肿胀；高浓度诱导快速和缓慢的细胞收缩。福斯高林（10^(-4)M）与特布他林（10^(-5)M）一样，诱导快速的细胞收缩，随后是缓慢的细胞收缩，并且苯扎米尔的存在增强了这种细胞体积的减小。另一方面，离子霉素（即使是低浓度；3×10^(-10)M离子霉素）诱导细胞收缩，之后细胞体积保持在平台水平。去除细胞外Ca2+消除了10^(-10)-10^(-8)M特布他林引起的细胞肿胀。去除细胞外Ca2+后，10^(-5)M特布他林诱导的最初快速细胞收缩变为短暂的，但我们仍然检测到与存在细胞外Ca2+时相似的缓慢细胞收缩。总体而言，在低浓度（10^(-10)-10^(-8)M）下，特布他林在FDLE细胞中诱导苯扎米尔敏感的细胞肿胀，这是cAMP和Ca2+依赖性的；高浓度（≥10^(-6)）诱导奎宁敏感的快速细胞收缩，这是Ca2+依赖性的；高浓度（≥10^(-7)）诱导缓慢的细胞收缩，这是cAMP依赖性的。这些发现表明，特布他林通过激活Na+和K+通道，通过细胞溶质cAMP和Ca2+调节FDLE细胞的细胞体积。
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