Kersting U, Napathorn S, Spring K R
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Membr Biol. 1993 Jul;135(1):11-8. doi: 10.1007/BF00234647.
Inhibition of the metabolism of arachidonic acid by the epoxygenase (cytochrome P-450) pathway with the inhibitor ketoconazole results in excessive cell swelling upon exposure to hyposmolality instead of the rapid and complete regulatory volume decrease (RVD) normally observed. NaCl entry from bathing solutions to cell interior was shown to cause this swelling, with Na influx occurring across the basolateral membrane and electrically silent Cl influx across the apical membrane. Ion substitution experiments show that the KCl efflux mediating RVD was unimpaired by ketoconazole, but was overwhelmed by the NaCl influx. Measurements of transepithelial fluid flux, Cl concentration, osmolality and pH showed that gallbladders treated with ketoconazole transiently secreted fluid rather than the normal absorption. We conclude that inhibition of arachidonic acid metabolism does not directly affect RVD by Necturus gallbladder, but that blockade of the epoxygenase pathway can have a profound influence on NaCl entry into gallbladder epithelial cells.
用抑制剂酮康唑抑制环氧合酶（细胞色素P-450）途径对花生四烯酸的代谢，会导致细胞在暴露于低渗环境时过度肿胀，而不是正常情况下观察到的快速且完全的调节性容积减小（RVD）。研究表明，从浴液进入细胞内的NaCl会导致这种肿胀，Na通过基底外侧膜内流，而Cl通过顶端膜进行电沉默内流。离子替代实验表明，介导RVD的KCl外流不受酮康唑影响，但被NaCl内流所掩盖。对跨上皮液体通量、Cl浓度、渗透压和pH的测量表明，用酮康唑处理的胆囊会短暂分泌液体而非正常吸收。我们得出结论：抑制花生四烯酸代谢不会直接影响美西螈胆囊的RVD，但环氧合酶途径的阻断会对NaCl进入胆囊上皮细胞产生深远影响。
