Non-peptide angiotensin II receptor antagonists. II. Pharmacology of S-8308.
Non-peptide angiotensin II receptor antagonists. II. Pharmacology of S-8308.
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非肽类血管紧张素II受体拮抗剂。
DOI：
10.1016/0014-2999(88)90465-7
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发表时间：
1988
影响因子：
5
通讯作者：
P. Timmermans
中科院分区：
文献类型：
--
作者：
A. Chiu;D. Carini;A. Johnson;D. McCall;W. Price;M. Thoolen;P. Wong;R. Taber;P. Timmermans
2-丁基-4-氯-1-（2-硝基苄基）咪唑-5-乙酸钠盐（S-8308）可抑制大鼠肾上腺皮质微粒体和培养的主动脉平滑肌细胞中标记的血管紧张素II（AII）与其受体位点的特异性结合，IC 50分别为15和4.5 μM。存在S-8308（15 μM）时，AII的解离常数增加2倍，结合位点总数不变。S-8308以浓度依赖性方式阻断AII（3 × 10− 8 M）诱导的大鼠主动脉环45 Ca 2+内流（IC 507 μM），竞争性抑制兔主动脉收缩反应（pA 2 = 5.74）。这种药物对AII具有高度特异性：它对α1-肾上腺素受体或Ca 2+通道没有亲和力，此外，它不会改变对去甲肾上腺素（10− 7 M）或KCl（55 mM）的收缩反应。在清醒的肾动脉结扎大鼠中，S-8308（30 mg/kg i. v.）结果表明，S-8308是一种弱的，但特异性和相容性，非肽类AII拮抗剂，在受体水平发挥其抑制作用。
2-Butyl-4-chloro-1-(2-nitrobenzyl)imidazole-5-acetic acid, sodium salt (S-8308), inhibited the specific binding of labeled angiotensin II (AII) to its receptor sites in rat adrenal cortical microsomes and in cultured aortic smooth muscle cells with IC50s of 15 and 4.5 μM, respectively. In the presence of S-8308 (15 μM) the dissociation constant for AII was increased 2-fold and the total number of binding sites was unaltered. In a concentration-dependent manner S-8308 blocked the45Ca2+influx induced by AII (3 × 10−8M) in rat aortic rings (IC507 μM) and the contractile response in rabbit aorta was competitively inhibited (pA2= 5.74). This agent was highly specific for AII: it showed no affinity forα1-adrenoceptors or Ca2+channels and in addition, it did not alter the contractile responses to norepinephrine (10−7M) or KCl (55 mM). In conscious renal artery-ligated rats, S-8308 (30 mg/kg i.v.) elicited a rapid decrease of mean arterial pressure with a duration of about 30 min. The results demonstrate that S-8308 is a weak, but specific and compatitive, non-peptide antagonist of AII exerting its inhibitory at the receptor level.
小鼠颌下肾素具有蛋白酶活性，可将人血浆非活性肾素原转化为活性形式。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Inagaki,T;Ohtsuki,K;Inagami,T
通讯作者：
Inagami,T