Norwood V F, Craig M R, Harris J M, Gomez R A
University of Virginia, Children's Medical Center, Charlottesville 22908, USA.
Am J Physiol. 1997 Feb;272(2 Pt 2):R662-8. doi: 10.1152/ajpregu.1997.272.2.R662.
Angiotensin II (ANG II) and its receptors, AT1 and AT2, may modulate kidney development. To define the temporal and spatial distribution of AT1 and AT2 receptors and their mRNAs during nephrogenesis, fetal, newborn, and adult rat kidneys were studied using reverse transcription-polymerase chain reaction and radioligand binding autoradiography. AT1 expression was minimal at embryonic day 14 (E14), highly expressed at E20, and persisted into adulthood. Conversely, AT2 expression was easily detected from E14 through postnatal day 7 but was undetectable by postnatal day 28. At E14, 76% of the receptors were AT2, 24% were AT1, and both were found in the undifferentiated mesenchyme. By E17, AT1 comprised 40% of the receptors and localized to mature nephron segments, whereas AT2 remained within both condensed mesenchyme and differentiating epithelia. The dissociation constants for AT1 and AT2 were 0.45 +/- 0.09 nM and 0.73 +/- 0.15 nM, respectively, at E17, similar to adult values. By E20, AT1 and AT2 colocalized to the outer medullary stripe, deep nephrons, medullary rays, and blood vessels, while AT2 continued to predominate in the actively differentiating cortex. The presence of both subtypes of receptors capable of binding ANG II during early nephrogenesis and the time-dependent and structure-specific regulation of receptor localization confirm a regulated developmental program for receptor expression and suggest important roles for AT1 and AT2 in renal morphogenesis.
血管紧张素II（ANG II）及其受体AT1和AT2可能调节肾脏发育。为了确定肾发生过程中AT1和AT2受体及其mRNA的时空分布，采用逆转录-聚合酶链反应和放射性配体结合放射自显影技术研究了胎鼠、新生鼠和成年大鼠的肾脏。AT1在胚胎第14天（E14）时表达最低，在E20时高表达，并持续到成年期。相反，AT2在E14至出生后第7天很容易检测到，但在出生后第28天则检测不到。在E14时，76%的受体是AT2，24%是AT1，两者都存在于未分化的间充质中。到E17时，AT1占受体的40%，并定位于成熟的肾单位节段，而AT2仍存在于浓缩的间充质和分化的上皮细胞中。E17时AT1和AT2的解离常数分别为0.45±0.09 nM和0.73±0.15 nM，与成年值相似。到E20时，AT1和AT2共定位于外髓质条纹、深部肾单位、髓放线和血管，而AT2在活跃分化的皮质中仍占主导地位。在早期肾发生过程中存在两种能够结合ANG II的受体亚型，以及受体定位的时间依赖性和结构特异性调节，证实了受体表达的调控发育程序，并提示AT1和AT2在肾脏形态发生中起重要作用。
