Morales M M, Nascimento D S, Capella M A, Lopes A G, Guggino W B
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, 21949-900, Brazil.
Pflugers Arch. 2001 Nov;443(2):202-11. doi: 10.1007/s004240100671.
The presence of both CFTR and ClC-2 proteins in the kidney suggest that they are involved in chloride transport along the nephron but their physiological roles in this organ are not known. To further understand the role of these chloride channels we studied Wistar rats subjected to dehydration for 2 days and also the homozygous Brattleboro rats, a strain of Long-Evans rats carrying an autosomal recessive mutation that leads to a deficiency of arginine-vasopressin (AVP) secretion in the plasma. The expression of CFTR was increased in the medulla of dehydrated Wistar rats and no variation was observed in the cortex. The expression of both ClC-2 and CFTR mRNAs was low in the renal cortex and medulla of the homozygous Brattleboro rats but returned to normal levels after AVP reposition. By the use of Madine-Darby canine kidney (MDCK) type I epithelial cells, it was observed that AVP (10(-8), 10(-7) and 10(-6) M) increased CFTR mRNA expression "in vitro" but no effect was observed when changes in the medium tonicity were caused by the addition of sucrose, NaCl, manitol or urea. The modulation of both CFTR and ClC-2 mRNA by AVP, the main hormone involved in the regulation of body fluid osmolality, suggests the participation of these two chloride channels in the renal tubule transcellular chloride transport modulated by AVP.
肾脏中同时存在囊性纤维化跨膜传导调节因子（CFTR）和氯离子通道蛋白2（ClC-2），这表明它们参与了沿肾单位的氯离子转运，但其在该器官中的生理作用尚不清楚。为了进一步了解这些氯离子通道的作用，我们研究了脱水2天的Wistar大鼠以及纯合子Brattleboro大鼠，后者是Long-Evans大鼠的一个品系，携带常染色体隐性突变，导致血浆中精氨酸加压素（AVP）分泌不足。脱水的Wistar大鼠髓质中CFTR的表达增加，而皮质中未观察到变化。纯合子Brattleboro大鼠肾皮质和髓质中ClC-2和CFTR mRNA的表达均较低，但在补充AVP后恢复到正常水平。通过使用I型马-达二氏犬肾（MDCK）上皮细胞，观察到AVP（10^(-8)、10^(-7)和10^(-6) M）“在体外”增加了CFTR mRNA的表达，但当通过添加蔗糖、氯化钠、甘露醇或尿素引起培养基张力变化时未观察到影响。参与调节体液渗透压的主要激素AVP对CFTR和ClC-2 mRNA的调节，表明这两种氯离子通道参与了由AVP调节的肾小管跨细胞氯离子转运。
