Angiotensin II and ACTH release: site of action and potency relative to corticotropin releasing factor and vasopressin.
Angiotensin II and ACTH release: site of action and potency relative to corticotropin releasing factor and vasopressin.
复制标题
血管紧张素 II 和 ACTH 释放：相对于促肾上腺皮质激素释放因子和加压素的作用部位和效力。
DOI：
10.1159/000123591
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发表时间：
1983
影响因子：
4.1
通讯作者：
Negro-Vilar,A
中科院分区：
文献类型：
--
作者：
Spinedi,E;Negro-Vilar,A
本研究旨在采用体内和体外结合的方法，测试血管紧张素II （AII）与其他具有促肾上腺皮质激素释放活性（CRA）的神经肽（如合成促肾上腺皮质激素释放因子（CRF）、精氨酸抗利尿素（AVP）和催产素（OXY））相比释放ACTH的能力；并确定是中心位点还是外周位点是肽的主要作用位点。在未麻醉的雄性大鼠体内注射AII(1和5 μg， ig)，最大剂量后血浆ACTH和β-内啡肽样免疫反应（β-end-LI）水平升高。然而，与0.5 μg的CRF或1 μg的AVP相比，这些反应并不明显。在中枢阻断大鼠（经氯丙嗪-吗啡-戊巴丁酯预处理）中注射AII（1或5 μg）均未引起ACTH或β-end-LI水平的升高，而0.5 μg的CRF或AVP均可使这两种激素升高数倍。利用雄性供体大鼠分散的垂体前叶细胞进行的体外研究表明，AII和AIII在10-8M或更大剂量下可增加ACTH释放。在相同条件下，CRF和AVP分别在10-10和10-9M时更大程度地刺激ACTH释放。另一方面，氧在10-8M有刺激作用。剂量反应研究表明，CRA的等级顺序为：CRF > AVP > OXY > AII = AIII。与CRF或AVP共孵育时，AII和AIII均表现出加性效应。血管紧张素受体阻滞剂saralasin可完全阻断AII或AIII体外的CRA及其加性效应。另一方面，Saralasin不影响CRF或AVP的CRA。随机循环雌性大鼠获得的分散垂体前叶细胞在ACTH释放方面对AII表现出更高的敏感性（最小有效剂量10-9M）。然而，反应的斜率与从男性供体中获得的细胞相似。这些研究表明：(1)AII能在体内释放ACTH和β-末端，但活性明显低于CRF或AVP；(2)全身给药AII对ACTH和β端释放的主要作用可能是由于中枢神经系统机制，而(3)AII的部分作用也可能涉及单独或与其他具有强效CRA的肽联合刺激垂体前叶中的特定AII受体。
The present studies were designed to test, using a combination of in vivo and in vitro paradigms, the potency of angiotensin II (AII) to release ACTH, in relation to that of other neural peptides with corticotropin-releasing activity (CRA), such as synthetic corticotropin releasing factor (CRF), arginine vasopressin (AVP) and oxytocin (OXY); and to determine whether a central or peripheral locus is the primary site of action of the peptide. Injection of AII (1 and 5 μg, i.p.) in intact unanesthetized male rats, resulted in an increase in plasma ACTH and β-endorphin-like immunoreactivy (β-end-LI) levels after the largest dose. The responses, however, were not as pronounced as those elicited by 0.5 μg of CRF or 1 μg of AVP. Injection of AII (i.v., 1 or 5 μg) in centrally blocked rats (pretreated with chlorpromazine-morphine-nembutal) failed to elicit any increase in either ACTH or β-end-LI levels, whereas 0.5 μg of either CRF or AVP increased both hormones several fold. In vitro studies using dispersed anterior pituitary cells obtained from male donor rats showed that AII as well as AIII could increase ACTH release at doses of 10-8M or larger. Under the same conditions, CRF and AVP stimulated ACTH release to a greater degree at 10-10and 10-9M, respectively. On the other hand, OXY was stimulatory at 10-8M. Dose-response studies indicated a rank order of CRA as follows: CRF > AVP > OXY > AII = AIII. Both AII and AIII showed additive effects when coincubated with either CRF or AVP. The CRA of AII or AIII in vitro, as well as their additive effects, were completely blocked by saralasin, an angiotensin receptor blocker. Saralasin, on the other hand, did not affect the CRA of CRF or AVP. Dispersed anterior pituitary cells obtained from randomly cycling female rats showed a higher sensitivity to AII in terms of ACTH release (minimal effective dose 10-9M). The slope of the response, however, was similar to that seen with cells obtained from male donors. These studies indicate that: (1) AII can release ACTH and β-end in vivo, but with an activity clearly lower than that of CRF or AVP; (2) the primary effect of systemically administered AII on ACTH and β-end release is probably due to a central nervous system mechanism(s), while, (3) a portion of the effects of AII may also involve stimulation of specific AII receptors in the anterior pituitary alone or in combination with other peptides with potent CRA.