Häuser W, Jöhren O, Saavedra J M
Section on Pharmacology, National Institute of Mental Health, Bethesda, MD 20892-1514, USA.
Eur J Pharmacol. 1998 May 1;348(1):101-14. doi: 10.1016/s0014-2999(98)00134-4.
We localized and characterized angiotensin II receptor subtypes (AT1 and AT2) in the mouse brain, with the use of autoradiography after incubation with [l25I][Sar1]-angiotensin II or [125I]CGP 42112 and displacement with selective angiotensin AT1 (losartan and candesartan) or angiotensin AT2 (CGP 42112(1) and PD 123319(2)) receptor ligands. In the mouse, the receptor subtype affinity for the different ligands was similar to that of the rat. The receptor subtype distribution was also similar to that in the rat, with some notable exceptions, such as the presence of angiotensin AT1 but not AT2 receptors in the locus coeruleus, and the expression of angiotensin AT1 receptors in the caudate putamen. These results confirm that careful consideration of the specific distribution of receptor subtypes in different species, even those closely related such as the mouse and the rat, should be conducted before meaningful comparisons could be proposed. Our data also form the basis for future studies of mouse models such as those with angiotensin receptor gene deficiencies.
我们利用与[¹²⁵I][Sar¹]-血管紧张素II或[¹²⁵I]CGP 42112孵育后的放射自显影技术，并使用选择性血管紧张素AT1（氯沙坦和坎地沙坦）或血管紧张素AT2（CGP 42112(1)和PD 123319(2)）受体配体进行置换，对小鼠脑中的血管紧张素II受体亚型（AT1和AT2）进行了定位和特性分析。在小鼠中，不同配体对受体亚型的亲和力与大鼠相似。受体亚型分布也与大鼠相似，但有一些显著例外，如蓝斑中存在血管紧张素AT1受体但不存在AT2受体，以及尾状壳核中血管紧张素AT1受体的表达。这些结果证实，在进行有意义的比较之前，应仔细考虑不同物种（即使是如小鼠和大鼠这样密切相关的物种）中受体亚型的特定分布。我们的数据也为未来对血管紧张素受体基因缺陷等小鼠模型的研究奠定了基础。
