EXPRESSION OF AT2-RECEPTORS IN THE DEVELOPING RAT FETUS
EXPRESSION OF AT2-RECEPTORS IN THE DEVELOPING RAT FETUS
复制标题
DOI：
10.1172/jci115395
复制
发表时间：
1991-09-01
影响因子：
15.9
通讯作者：
KALINYAK, JE
中科院分区：
文献类型：
--
作者：
GRADY, EF;SECHI, LA;KALINYAK, JE
血管紧张素II主要因其对血压和电解质稳态的影响而为人所知，但最近的研究表明，血管紧张素II可能在调节细胞生长方面发挥作用。本研究旨在鉴定在胎儿和新生儿发育过程中表达的血管紧张素II受体亚型，并表征其细胞定位。对胎鼠和新生鼠矢状面冷冻切片进行原位受体结合实验，通过胶片和乳剂放射自显像显示结合的I-125-[Sar1， Ile8]-血管紧张素II。E11（胚胎第11天）检测到结合的放射配体，E19-21发生最大的结合。放射配体结合在出生后30分钟保持不变，而在分娩后12小时观察到明显而稳定的下降。高度丰富的血管紧张素II受体通过与AT2受体拮抗剂PD123177 （10(-7) M）的放射性配体结合显著减少而被证明是AT2受体，而AT1受体拮抗剂DuP 753 （10(-5) M）几乎没有影响。乳剂放射自显像显示，在肠和胃粘膜下层的未分化间质、视网膜周围的结缔组织和脉络膜、发育中的软骨、隔膜和舌附近的真皮下间质中存在放射配体结合。出生72 h后，舌背真皮下区发现残留的AT2受体。在E13时胎盘中检测到AT1受体，在E19-21时主动脉、肾脏、肺、肝和肾上腺中检测到AT1受体，与成人分布一致。胎儿间质中AT2受体的瞬时表达提示血管紧张素II在胎儿发育中的作用。
Angiotensin II is known primarily for its effects on blood pressure and electrolyte homeostasis, but recent studies suggest that angiotensin II may play a role in the regulation of cellular growth. This study was undertaken to identify the angiotensin II receptor subtypes expressed during fetal and neonatal development and to characterize their cellular localization. Using an in situ receptor binding assay on sagittal frozen sections of fetal and neonatal rats, bound I-125-[Sar1, Ile8]-angiotensin II was visualized by film and emulsion autoradiography. Bound radioligand was detected by E11 (embryonic day 11) and maximal binding occurred by E19-21. Radioligand binding remained unaltered 30 min after birth, whereas a noticeable and stable decrease was observed 12 h postparturition. The highly abundant angiotensin II receptors were shown to be AT2 by the marked reduction in radioligand binding achieved with PD123177 (10(-7) M), a specific AT2 receptor antagonist, whereas DuP 753 (10(-5) M), an AT1 receptor antagonist, had little effect. Emulsion autoradiography showed radioligand binding in the undifferentiated mesenchyme of the submucosal layers of the intestine and stomach, connective tissue and choroid surrounding the retina, subdermal mesenchyme adjacent to developing cartilage, diaphragm, and tongue. Residual AT2 receptors were found on the dorsal subdermal region of the tongue 72 h after birth. AT1 receptors were detected in the placenta at E13 and in the aorta, kidney, lung, liver, and adrenal gland at E19-21, consistent with an adult distribution. The transient expression of AT2 receptors in the mesenchyme of the fetus suggests a role of angiotensin II in fetal development.