Jard S, Gaillard R C, Guillon G, Marie J, Schoenenberg P, Muller A F, Manning M, Sawyer W H
Mol Pharmacol. 1986 Aug;30(2):171-7.
The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from the determination of the concentration-dependent inhibition of [3H]vasopressin binding. In parallel experiments the corticotropin (or anti-corticotropin)-releasing activities of the tested peptides were determined on freshly dispersed rat adenohypophyseal cells. All peptides tested which were found to be antagonists of the vasopressor and antidiuretic responses to vasopressin in vivo behaved as antagonists of vasopressin-induced corticotropin release. There was a close correlation between the relative affinities of the analogues tested for binding to adenohypophyseal membranes and their relative potencies in inhibiting vasopressin-induced corticotropin release, indicating that the detected vasopressin-binding sites are the receptors involved in the vasopressin effect on corticotropin secretion. No correlation could be demonstrated between anti-corticotropin-releasing activities and either anti-antidiuretic or antivasopressor potencies of the antagonists tested. A direct comparison of the ligand specificities of adenohypophyseal receptors on the one hand, and V1 (hepatic) and V2 (renal) receptors on the other hand, showed that most of the antagonists discriminated very efficiently between adenohypophyseal and either hepatic or renal receptors. The selectivity index reaches values as high as 260,000 for desGly(NH2)9 [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-D-O-ethyl-tyrosine, 4-valine] arginine vasopressin. It is concluded that adenohypophyseal receptors represent a novel type of vasopressin receptors. Based on the observation that adenohypophyseal receptors, like hepatic or vascular V1 receptors, do not appear to be coupled to adenylate cyclase, we propose that adenohypophyseal receptors could be designated as V1b receptors as opposed to the V1a receptors previously characterized on liver and blood vessels.
将大鼠腺垂体血管加压素受体的配体特异性与V1和V2型外周受体的配体特异性进行了直接比较。为此，使用了一系列最近设计的15种血管加压素拮抗剂。这些拮抗剂对大鼠腺垂体膜的亲和力是通过测定[3H]血管加压素结合的浓度依赖性抑制来推导的。在平行实验中，在新鲜分散的大鼠腺垂体细胞上测定了受试肽的促肾上腺皮质激素（或抗促肾上腺皮质激素）释放活性。所有测试的肽在体内被发现是血管加压素升压和抗利尿反应的拮抗剂，它们表现为血管加压素诱导的促肾上腺皮质激素释放的拮抗剂。受试类似物与腺垂体膜结合的相对亲和力与其抑制血管加压素诱导的促肾上腺皮质激素释放的相对效力之间存在密切相关性，这表明检测到的血管加压素结合位点是参与血管加压素对促肾上腺皮质激素分泌作用的受体。在所测试的拮抗剂的抗促肾上腺皮质激素释放活性与抗利尿或抗升压效力之间未发现相关性。一方面对腺垂体受体的配体特异性与另一方面的V1（肝脏）和V2（肾脏）受体的配体特异性进行直接比较，结果表明大多数拮抗剂能够非常有效地区分腺垂体受体与肝脏或肾脏受体。对于去甘氨酰胺（NH2）9 [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]精氨酸血管加压素，选择性指数高达260,000。得出的结论是，腺垂体受体代表一种新型的血管加压素受体。基于腺垂体受体与肝脏或血管V1受体一样似乎不与腺苷酸环化酶偶联的观察结果，我们建议将腺垂体受体指定为V1b受体，以区别于先前在肝脏和血管中鉴定的V1a受体。
