Seltzer A M, Zorad S, Saavedra J M
Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Brain Res. 1995 Dec 24;705(1-2):24-30. doi: 10.1016/0006-8993(95)01100-5.
The aim of our study was to determine the second messenger systems for angiotensin II in the rat median eminence. Angiotensin II AT1 receptors are highly expressed in the median eminence and binding is selectively inhibited by the guanine nucleotide GTP gamma S, indicating possible coupling to G-proteins. In male rats, angiotensin II increased phosphatidylinositol hydrolysis about 45% over basal values, with an EC50 of about 2.7 nM. This effect was antagonized by 10 microM losartan, the selective AT1 antagonist, but not by the AT2 competitor PD 123319. Conversely, angiotensin II, 1 microM, did not alter basal or forskolin-stimulated cAMP production, and failed to influence cGMP production. These results support a role for angiotensin II, through stimulation of AT1 receptors and increased phosphatidylinositol hydrolysis, in the median eminence. Angiotensin II increased the phosphatidylinositol hydrolysis not only in male rats but also in ovariectomized rats, with or without estrogen-progesterone replacement. However, angiotensin II (up to 1 microM) failed to increase the phosphatidylinositol hydrolysis in randomly selected intact female rats. Estrogen treatment did not alter the number or affinity of median eminence AT1 receptors in ovariectomized rats. The increase in phosphatidylinositol hydrolysis resulting from stimulation of median eminence AT1 receptors appears to be sexually dimorphic, but hormonal manipulations failed to point to a role for reproductive hormones in this phenomenon.
我们研究的目的是确定大鼠正中隆起中血管紧张素II的第二信使系统。血管紧张素II的AT1受体在正中隆起中高度表达，并且鸟嘌呤核苷酸GTPγS可选择性抑制其结合，这表明可能与G蛋白偶联。在雄性大鼠中，血管紧张素II使磷脂酰肌醇水解比基础值增加约45%，半数有效浓度（EC50）约为2.7 nM。这种作用可被10 μM的氯沙坦（一种选择性AT1拮抗剂）拮抗，但不能被AT2竞争性拮抗剂PD 123319拮抗。相反，1 μM的血管紧张素II不会改变基础或福司可林刺激的环磷酸腺苷（cAMP）生成，也不会影响环磷酸鸟苷（cGMP）生成。这些结果支持血管紧张素II通过刺激AT1受体并增加磷脂酰肌醇水解在正中隆起中发挥作用。血管紧张素II不仅能增加雄性大鼠的磷脂酰肌醇水解，在去卵巢大鼠中，无论是否补充雌激素 - 孕激素，也能增加其磷脂酰肌醇水解。然而，高达1 μM的血管紧张素II未能增加随机选取的完整雌性大鼠的磷脂酰肌醇水解。雌激素处理并未改变去卵巢大鼠正中隆起AT1受体的数量或亲和力。刺激正中隆起AT1受体导致的磷脂酰肌醇水解增加似乎具有性别差异，但激素处理未能表明生殖激素在这一现象中发挥作用。
