Yasui M, Marples D, Belusa R, Eklöf A C, Celsi G, Nielsen S, Aperia A
Department of Woman and Child Health, St. Göran's Children's Hospital, Karolinska Institute, Stockholm, Sweden.
Am J Physiol. 1996 Aug;271(2 Pt 2):F461-8. doi: 10.1152/ajprenal.1996.271.2.F461.
The capacity to concentrate urine develops progressively during postnatal life in most mammalian species. Here we have examined whether low expression of the arginine vasopressin (AVP)-activated water channel aquaporin-2 (AQP-2) may be a limiting factor for the concentrating capacity in the infant rats. Urine osmolality in response to 24-h dehydration increased significantly from 10 to 40 days of age. The most rapid increase occurred during the weaning period, i.e., days 15-20. A similar developmental pattern was observed for AQP-2 mRNA levels in the renal medulla. AQP-2 protein levels also increased markedly from day 10 to 40. Immunohistochemistry revealed that AQP-2 was exclusively located in collecting duct principal cells both in infant and adult rats but that the signal was much weaker in infants. To further examine the relationship between urinary concentrating capacity and AQP-2 expression, we treated rats with a single injection of betamethasone, which is known to accelerate maturation in several organs. Twenty-four hours after treatment, there was an increase in urine osmolality, renal medullary AQP-2 mRNA, and AQP-2 protein levels in infant but not in adult rats. A single injection of a specific V2 agonist caused within 6 h significant increase of AQP-2 mRNA in both infant and adult. The expression of the mRNA of three other transporters involved in the concentrating process, medullary Na(+)-K(+)-ATPase alpha-subunit, Na-K-2Cl cotransporter, and epithelial chloride channel also increased during the weaning period and were upregulated by glucocorticoids. We conclude that there is a well-synchronized development of the many of the components that determine the concentrating capacity and that the low expression of AQP-2 is one of the limiting factors for low concentrating capacity in infants.
在大多数哺乳动物出生后的生命过程中，尿液浓缩能力是逐步发展的。在此，我们研究了精氨酸加压素（AVP）激活的水通道蛋白2（AQP - 2）低表达是否可能是幼鼠浓缩能力的限制因素。对24小时脱水的反应中，尿渗透压在10至40日龄时显著增加。最快速的增加发生在断奶期，即15 - 20日龄。肾髓质中AQP - 2 mRNA水平也观察到类似的发育模式。AQP - 2蛋白水平从第10天到40天也显著增加。免疫组织化学显示，AQP - 2仅位于幼鼠和成年大鼠的集合管主细胞中，但幼鼠中的信号要弱得多。为了进一步研究尿液浓缩能力与AQP - 2表达之间的关系，我们用单次注射倍他米松处理大鼠，已知倍他米松可加速多个器官的成熟。处理24小时后，幼鼠的尿渗透压、肾髓质AQP - 2 mRNA和AQP - 2蛋白水平增加，而成年大鼠则未增加。单次注射特异性V2激动剂在6小时内可使幼鼠和成年大鼠的AQP - 2 mRNA均显著增加。参与浓缩过程的其他三种转运蛋白，髓质Na(+) - K(+) - ATP酶α亚基、Na - K - 2Cl共转运体和上皮氯通道的mRNA表达在断奶期也增加，并被糖皮质激素上调。我们得出结论，决定浓缩能力的许多成分存在良好同步的发育，并且AQP - 2的低表达是幼鼠浓缩能力低的限制因素之一。
