Department of Physiology, University of Tübingen, Germany.
Kidney Blood Press Res. 2013;37(4-5):514-20. doi: 10.1159/000355731. Epub 2013 Nov 16.
BACKGROUND/AIMS: The Janus kinase 3 JAK3 participates in the signaling of immune cells. Lack of JAK3 triggers inflammatory bowel disease, which in turn has been shown to affect intestinal activity of the epithelial Na(+) channel ENaC and thus colonic sodium absorption. At least in theory, inflammatory bowel disease in JAK3-deficient mice could lead to intestinal salt loss compromizing extracellular volume maintenance and blood pressure regulation. The present study thus explored whether JAK3 deficiency impacts on colonic ENaC activity, fecal Na(+) exretion, blood pressure and extracellular fluid volume regulation.
Experiments were performed in gene-targeted mice lacking functional JAK3 (jak3(-/-)) and in wild type mice (jak3(+/+)). Colonic ENaC activity was estimated from amiloride-sensitive current in Ussing chamber experiments, fecal, serum and urinary Na(+) concentration by flame photometry, blood pressure by the tail cuff method and serum aldosterone levels by immunoassay.
The amiloride (50 µM)-induced deflection of the transepithelial potential difference was significantly lower and fecal Na(+) excretion significantly higher in jak3(-/-) mice than in jak3(+/+) mice. Moreover, systolic arterial blood pressure was significantly lower and serum aldosterone concentration significantly higher in jak3(-/-) mice than in jak3(+/+) mice. Both, absolute and fractional renal Na(+) excretion were significantly lower in jak3(-/-) mice than in jak3(+/+) mice.
JAK3 deficiency leads to impairment of colonic ENaC activity with intestinal Na(+) loss, decrease of blood pressure, increased aldosterone release and subsequent stimulation of renal tubular Na(+) reabsorption.
背景/目的：Janus 激酶 3（JAK3）参与免疫细胞的信号转导。JAK3 的缺失会引发炎症性肠病，而炎症性肠病反过来又会影响上皮钠通道（ENaC）的肠道活性，从而导致结肠钠吸收。至少从理论上讲，JAK3 缺陷小鼠的炎症性肠病可能导致肠道盐丢失，损害细胞外液容量的维持和血压调节。本研究因此探讨了 JAK3 缺乏是否会影响结肠 ENaC 活性、粪便 Na+排泄、血压和细胞外液容量调节。
在缺乏功能性 JAK3（jak3(-/-)）的基因靶向小鼠和野生型小鼠（jak3(+/+)）中进行实验。通过 Ussing 室实验测量阿米洛利敏感电流来估计结肠 ENaC 活性，通过火焰光度法测量粪便、血清和尿液中的 Na+浓度，通过尾套法测量血压，通过免疫测定法测量血清醛固酮水平。
与 jak3(+/+)小鼠相比，阿米洛利（50µM）诱导的跨上皮电位差的偏转明显更低，粪便 Na+排泄明显更高。此外，jak3(-/-)小鼠的收缩压明显更低，血清醛固酮浓度明显更高。与 jak3(+/+)小鼠相比，jak3(-/-)小鼠的绝对和分数肾 Na+排泄均明显降低。
JAK3 缺乏导致结肠 ENaC 活性受损，出现肠道 Na+丢失，血压降低，醛固酮释放增加，随后刺激肾小管 Na+重吸收。
