vom Dahl S, Hallbrucker C, Lang F, Häussinger D
Medizinische Universitätsklinik, Freiburg, Federal Republic of Germany.
Biochem J. 1991 Nov 15;280 ( Pt 1)(Pt 1):105-9. doi: 10.1042/bj2800105.
The effect of hormones on cell volume was studied in isolated perfused rat liver by assessing the intracellular water space as the difference between a [3H]inulin- and a [14C]urea-accessible space. The intracellular water space (control value 559 +/- 7 microliters/g of liver; n = 88) increased on addition of insulin (35 nM) or phenylephrine (5 microM) by 12 or 8% respectively, whereas it decreased with cyclic AMP (cAMP; 50 microM), glucagon (100 nM) or adenosine (50 microM) by 9, 13 or 6% respectively. Both insulin and glucagon exerted half-maximal effects on cell volume and cellular K+ balance at hormone concentrations found physiologically in the portal vein. Adenosine-induced cell shrinkage was explained by a net K+ release from the liver. Phenylephrine (5 microM) led to cell swelling by about 8%, which was additive to insulin-induced swelling. Extracellular ATP (20 microM) induced cell shrinkage by about 6%; this was additive to adenosine-induced shrinkage. Vasopressin (15 nM) did not appreciably change cell volume, but induced marked cell shrinkage when glucagon or cAMP was present. Insulin- and phenylephrine-induced cell swelling was counteracted by cAMP. Hormone-induced changes of intracellular water space could sufficiently explain accompanying liver mass changes induced by glucagon, cAMP, adenosine or vasopressin, but not those by phenylephrine and extracellular ATP. The data show that liver cell volume is subject to hormonal regulation, in part owing to modification of cellular K+ balance. Glucagon- and insulin-induced cell volume changes occur already in the presence of physiological hormone concentrations. The effects of Ca2(+)-mobilizing hormones on cell volume are not uniform. In view of the recently established role of cell volume changes in modulating liver cell function, the present findings open a new perspective on the mechanisms of hormone action in liver, underlining our previous hypothesis that cell volume changes may represent a 'second messenger' of hormone action.
通过评估细胞内水空间（即[³H]菊粉可及空间与[¹⁴C]尿素可及空间之差），在离体灌注大鼠肝脏中研究了激素对细胞体积的影响。细胞内水空间（对照值为559±7微升/克肝脏；n = 88）在添加胰岛素（35 nM）或去氧肾上腺素（5 μM）后分别增加了12%或8%，而在添加环磷酸腺苷（cAMP；50 μM）、胰高血糖素（100 nM）或腺苷（50 μM）后分别减少了9%、13%或6%。胰岛素和胰高血糖素在门静脉中生理浓度的激素水平下，对细胞体积和细胞钾平衡均产生半数最大效应。腺苷诱导的细胞收缩是由肝脏净钾释放所致。去氧肾上腺素（5 μM）导致细胞肿胀约8%，这与胰岛素诱导的肿胀具有相加作用。细胞外ATP（20 μM）诱导细胞收缩约6%；这与腺苷诱导的收缩具有相加作用。血管加压素（15 nM）对细胞体积无明显影响，但在存在胰高血糖素或cAMP时会诱导明显的细胞收缩。cAMP可抵消胰岛素和去氧肾上腺素诱导的细胞肿胀。激素诱导的细胞内水空间变化足以解释胰高血糖素、cAMP、腺苷或血管加压素引起的肝脏质量变化，但不能解释去氧肾上腺素和细胞外ATP引起的变化。数据表明，肝细胞体积受激素调节，部分原因是细胞钾平衡的改变。胰高血糖素和胰岛素诱导的细胞体积变化在生理激素浓度下就已出现。钙动员激素对细胞体积的影响并不一致。鉴于最近确立的细胞体积变化在调节肝细胞功能中的作用，本研究结果为肝脏中激素作用机制开辟了新视角，强调了我们之前的假设，即细胞体积变化可能代表激素作用的“第二信使”。
