Sobel D O
Neuroendocrinology. 1983;36(4):249-53. doi: 10.1159/000123463.
The ACTH-releasing activities of angiotensin I, angiotensin III, [des (Asp1,Arg2)]Ang II, and [des (Asp1,Arg2,VAl3)]Ang II was compared with that of angiotensin II (Ang II) in rat pituitary cell monolayer culture. In addition, the role of known Ang II receptor antagonists, glucocorticoid and of antiadrenergic and antiserotonergic compounds on Ang II induced ACTH release was investigated. The relative potencies of the angiotensin analogs were: Ang II greater than Ang III greater than [des (Asp1,Arg2)]Ang II. [Des (Asp1,Arg2,Val3)]Ang II was nonstimulatory. Angiotensin I-induced ACTH was completely inhibited by the addition of converting enzyme inhibitor SQ20881. A similar dose-related inhibition of Ang II-stimulated ACTH release by [Sar1,Ala8]Ang II and [Sar1,Gly8]Ang II was demonstrated. corticosterone (5 nM) decreased Ang II (10 nM) mediated ACTH release to control values while dibenzyline (10 microM), an alpha-adrenergic antagonist and cyproheptadine (10 microM), a serotonin antagonist did not alter the stimulation of ACTH by Ang II. This study suggests (1) the N-terminal amino acids of Ang II are important for the ACTH stimulatory action of Ang II, (2) [Sar1,Ala8]Ang II and [Sar1,Gly8]Ang II are specific Ang II antagonists at the pituitary level towards the ACTH releasing effect of Ang II, and (3) corticosterone inhibits the in vitro pituitary ACTH release by Ang II while dibenzyline and cyproheptadine have no effect.
在大鼠垂体细胞单层培养中，比较了血管紧张素I、血管紧张素III、[去（天冬氨酸1，精氨酸2）]血管紧张素II和[去（天冬氨酸1，精氨酸2，缬氨酸3）]血管紧张素II与血管紧张素II（Ang II）的促肾上腺皮质激素（ACTH）释放活性。此外，还研究了已知的Ang II受体拮抗剂、糖皮质激素以及抗肾上腺素能和抗血清素能化合物对Ang II诱导的ACTH释放的作用。血管紧张素类似物的相对效力为：Ang II＞Ang III＞[去（天冬氨酸1，精氨酸2）]Ang II。[去（天冬氨酸1，精氨酸2，缬氨酸3）]Ang II无刺激作用。添加转化酶抑制剂SQ20881可完全抑制血管紧张素I诱导的ACTH释放。[Sar1，Ala8]Ang II和[Sar1，Gly8]Ang II对Ang II刺激的ACTH释放具有类似的剂量相关抑制作用。皮质酮（5 nM）可将Ang II（10 nM）介导的ACTH释放降低至对照值，而α-肾上腺素能拮抗剂二苯苄胺（10 μM）和血清素拮抗剂赛庚啶（10 μM）不会改变Ang II对ACTH的刺激作用。本研究表明：（1）Ang II的N端氨基酸对Ang II的ACTH刺激作用很重要；（2）[Sar1，Ala8]Ang II和[Sar1，Gly8]Ang II在垂体水平是针对Ang II释放ACTH作用的特异性Ang II拮抗剂；（3）皮质酮可抑制Ang II在体外诱导的垂体ACTH释放，而二苯苄胺和赛庚啶则无作用。
