Characterization of angiotensin II receptor subtypes in rat heart.
Characterization of angiotensin II receptor subtypes in rat heart.
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DOI：
10.1161/01.res.71.6.1482
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发表时间：
1992-12
影响因子：
20.1
通讯作者：
L. A. Sechi;C. A. Griffin;E. F. Grady;J E Kalinyak;M. Schambelan
中科院分区：
文献类型：
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作者：
L. A. Sechi;C. A. Griffin;E. F. Grady;J E Kalinyak;M. Schambelan
血管紧张素II通过与特异性膜受体结合对哺乳动物心脏发挥正性肌力和变时作用。最近，两种亚型的血管紧张素II受体（AT 1和AT 2）已区分使用非肽拮抗剂氯沙坦（以前称为DuP 753）和PD 123177。为了评价大鼠心脏血管紧张素II受体的组织分布和亚型，我们对成年Sprague-Dawley大鼠（10和14周龄）的组织切片进行了125 I-[Sar 1，Ile 8]血管紧张素II原位结合试验。通过与未标记的[Sar 1]血管紧张素II竞争验证结合特异性。AT 1和AT 2受体的分布分别通过与氯沙坦和PD 123177的竞争来确定，并且受体的密度通过乳剂放射自显影来定量。血管紧张素II受体广泛分布于整个心脏，每种受体亚型约占特异性结合的50%。结合密度在心房、右心室和左心室、室间隔和窦房结中相当，而在房室结中显著更大。AT 1受体似乎与胍核苷酸调节蛋白相互作用，因为GTP-γ-S导致放射性配体从该受体解离。相反，AT 2受体似乎不直接与鸟嘌呤核苷酸调节蛋白相互作用，因为放射性配体从该受体亚型解离不受GTP-γ-S的影响。由于血管紧张素II已被报道在几种组织中具有生长促进作用，我们研究了胎儿（胚胎第16和19天）和新生儿（1-，2-，3-和10天）大鼠的血管紧张素II受体。（250字处删节）
Angiotensin II exerts positive inotropic and chronotropic effects on the mammalian heart by binding to specific membrane receptors. Recently, two subtypes of angiotensin II receptors (AT1 and AT2) have been distinguished by using the nonpeptide antagonists losartan (previously known as DuP 753) and PD123177. To evaluate the tissue distribution and subtypes of angiotensin II receptors in rat heart, we performed a 125I-[Sar1,Ile8]angiotensin II in situ binding assay on tissue sections obtained from adult Sprague-Dawley rats (10 and 14 weeks old). Binding specificity was verified by competition with unlabeled [Sar1]angiotensin II. Distribution of AT1 and AT2 receptors was determined by competition with losartan and PD123177, respectively, and the density of the receptors was quantified by emulsion autoradiography. Angiotensin II receptors were widely distributed throughout the heart, with each receptor subtype accounting for approximately 50% of the specific binding. Binding density was comparable in the atria, right and left ventricles, intraventricular septum, and sinoatrial node, whereas it was significantly greater in the atrioventricular node. The AT1 receptor appears to interact with guanidine nucleotide regulatory proteins, because GTP-gamma-S causes dissociation of the radioligand from this receptor. In contrast, the AT2 receptor does not appear to directly interact with guanine nucleotide regulatory proteins, inasmuch as radioligand dissociation from this receptor subtype is not affected by GTP-gamma-S. Because angiotensin II has been reported to have growth-potentiating effects in several tissues, we examined angiotensin II receptors in fetal (embryonic days 16 and 19) and neonatal (1-, 2-, 3-, and 10-day-old) rats.(ABSTRACT TRUNCATED AT 250 WORDS)