Bernardini R, Chiarenza A, Kamilaris T C, Renaud N, Lempereur L, Demitrack M, Gold P W, Chrousos G P
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Md.
Neuroendocrinology. 1994 Nov;60(5):503-8. doi: 10.1159/000126787.
Arginine-vasopressin (AVP) is regarded as a potent stimulator of pituitary adrenocorticotropin (ACTH) secretion and participates therefore in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis function in concert with the physiological activator of the axis, hypothalamic corticotropin-releasing hormone (CRH). We examined the effects of AVP and/or three synthetic V1b receptor antagonists on the activity of the HPA axis in vivo and in vitro in the rat. AVP was injected intravenously to Sprague-Dawley rats (1 microgram/rat) through an indwelling jugular catheter. AVP stimulated ACTH release, with maximal effect 10 min after injection. Intravenous injection of three V1b antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin (d(CH2)5[Tyr(Et2)]VAVP (WK 1-1), 9-desglycine[1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin desGly9d(CH2)5 [Tyr(Et2)]-VAVP (WK 3-6), and 9-desglycine [1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid),2-D-(O-ethyl)tyrosine, 4-valine ] arginine vasopressin des Gly9d(CH2)5[D-Tyr(Et2)]VAVP (AO 3-21), prevented AVP-stimulated ACTH secretion. Explanted rat hypothalami incubated in vitro with graded concentrations of AVP (10(-14)-10(-5) M) secreted immunoreactive CRH (iCRH) in a concentration-dependent fashion. Maximal stimulatory effect occurred at the concentration of 10(-6) M. Incubation of hypothalami with WK 1-1, WK3-6, or AO 3-21 (10(-6) M) prevented AVP-stimulated iCRH secretion. Results suggest that AVP plays a relevant, multiple role in the activation of the HPA axis in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
精氨酸加压素（AVP）被视为垂体促肾上腺皮质激素（ACTH）分泌的强效刺激剂，因此与该轴的生理激活剂——下丘脑促肾上腺皮质激素释放激素（CRH）协同参与下丘脑-垂体-肾上腺（HPA）轴功能的调节。我们在大鼠体内和体外研究了AVP和/或三种合成V1b受体拮抗剂对HPA轴活性的影响。通过留置的颈静脉导管向Sprague-Dawley大鼠静脉注射AVP（1微克/只）。AVP刺激ACTH释放，注射后10分钟效果最大。静脉注射三种V1b拮抗剂，[1-（β-巯基-β，β-环戊亚甲基丙酸），2-O-乙基酪氨酸，4-缬氨酸]精氨酸加压素（d（CH2）5[Tyr（Et2）]VAVP（WK 1-1）、9-去甘氨酸[1-（β-巯基-β，β-环戊亚甲基丙酸），2-O-乙基酪氨酸，4-缬氨酸]精氨酸加压素desGly9d（CH2）5 [Tyr（Et2）]-VAVP（WK 3-6）和9-去甘氨酸[1-（β-巯基-β，β-环戊亚甲基丙酸），2-D-（O-乙基）酪氨酸，4-缬氨酸]精氨酸加压素des Gly9d（CH2）5[D-Tyr（Et2）]VAVP（AO 3-21），可阻止AVP刺激的ACTH分泌。用不同浓度的AVP（10^-14 - 10^-5 M）在体外孵育分离出的大鼠下丘脑，下丘脑以浓度依赖的方式分泌免疫反应性CRH（iCRH）。最大刺激效应出现在10^-6 M浓度时。用WK 1-1、WK3-6或AO 3-21（10^-6 M）孵育下丘脑可阻止AVP刺激的iCRH分泌。结果表明，AVP在大鼠HPA轴激活中发挥着相关的多重作用。（摘要截选至250字）
