Watanabe T, Oki Y, Orth D N
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Endocrinology. 1989 Oct;125(4):1921-31. doi: 10.1210/endo-125-4-1921.
We have examined the actions and interactions of arginine vasopressin (AVP), angiotensin-II (AII), and oxytocin (OT) on the ACTH secretory response of dispersed rat anterior pituitary cells in a microperifusion system. There was a dose-dependent ACTH secretory response to a 3-min perifusion of AII which reached its maximum 10 sec after the cells were exposed to AII and fell rapidly to baseline within 2 min, despite continued infusion of AII. This brief spike type of pattern is similar to that produced by AVP, but different from the sustained plateau response induced by CRF. The threshold stimulating concentration of AII was about 10(-9) M; the maximally stimulating concentration was not defined, but was 10(-6) M or more. The initial ACTH response to OT was similar, but fell to a plateau 2 min after the cells were exposed to OT and remained constant until perifusion with OT was stopped, after which it fell rapidly to baseline. The threshold stimulating concentration of OT was 10(-8) M; the maximally stimulating concentration was not defined, but was 10(-6) M or more. The ACTH secretory response to 10(-8) M AII was greatly diminished when cells were exposed to 10(-6) AVP or 10(-6) M OT before AII infusion. However, prior exposure to AII had no effect on the magnitude of the ACTH secretory response to either AVP or OT. The effects of simultaneous perifusion of AII and AVP and of AII and OT were additive. When AVP and OT were perifused sequentially, the ACTH secretory response to the peptide that was infused second was completely abolished. Furthermore, the combination of AVP and OT stimulated no greater response than either agent alone. When cells were perifused with the combination of 10(-7) M OT and 10(-7)- to 10(-5)-M concentrations of two potent AVP V1 receptor antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]-Arg8-vasopressin and [1-deaminopenicillamine-2-(O-methyl)tyrosine]-Arg8-vasopressin, both phases of the response to OT were progressively and almost completely inhibited. The initial spike phase was inhibited at lower antagonist concentrations than the sustained plateau phase.(ABSTRACT TRUNCATED AT 400 WORDS)
我们在微灌流系统中研究了精氨酸加压素（AVP）、血管紧张素II（AII）和催产素（OT）对分散的大鼠垂体前叶细胞促肾上腺皮质激素（ACTH）分泌反应的作用及相互作用。对AII进行3分钟灌流时，ACTH分泌反应呈剂量依赖性，在细胞接触AII后10秒达到最大值，尽管持续灌注AII，但在2分钟内迅速降至基线。这种短暂的峰值型模式与AVP产生的模式相似，但与促肾上腺皮质激素释放因子（CRF）诱导的持续平台反应不同。AII的阈值刺激浓度约为10^(-9) M；最大刺激浓度未确定，但为10^(-6) M或更高。对OT的初始ACTH反应相似，但在细胞接触OT后2分钟降至平台期，并保持恒定，直到停止OT灌流，之后迅速降至基线。OT的阈值刺激浓度为10^(-8) M；最大刺激浓度未确定，但为10^(-6) M或更高。在AII灌注前，当细胞接触10^(-6) AVP或10^(-6) M OT时，对10^(-8) M AII的ACTH分泌反应大大减弱。然而，预先接触AII对AVP或OT的ACTH分泌反应幅度没有影响。同时灌注AII和AVP以及AII和OT的作用是相加的。当依次灌注AVP和OT时，对第二种灌注肽的ACTH分泌反应完全被消除。此外，AVP和OT的组合刺激的反应并不比单独使用任何一种药物更大。当细胞用10^(-7) M OT和10^(-7)至10^(-5) M浓度的两种强效AVP V1受体拮抗剂[1-(β-巯基-β,β-环戊亚甲基丙酸),2-(O-甲基)酪氨酸]-精氨酸8-加压素和[1-脱氨青霉胺-2-(O-甲基)酪氨酸]-精氨酸8-加压素的组合进行灌流时，对OT反应的两个阶段都逐渐且几乎完全被抑制。初始峰值阶段在比持续平台期更低的拮抗剂浓度下被抑制。（摘要截于400字）
