Claire M, Rafestin-Oblin M E, Michaud A, Roth-Meyer C, Corvol P
Endocrinology. 1979 Apr;104(4):1194-200. doi: 10.1210/endo-104-4-1194.
Two new aldosterone antagonists, K-prorenoate [potassium 3(17 beta-hydroxy-6 beta, 7 beta-methylen-3-oxo-4-androsten-17 alpha-yl)propionate] and prorenone [3(17 beta-hydroxy-6 beta, 7 beta-methylen-3-oxo-4-androsten-17 alpha-yl) propionic acid gamma-lactone], its lactonic form, were studied in rat kidney using in vitro systems. Study of [3H]prorenone binding by a recently developed computer method indicated a high affinity, low capacity class of sites which are, seemingly, mineralocorticoid receptors. In competition experiments performed on [3H]aldosterone- and [3H]dexamethasone-binding sites, prorenone appeared to be a good competitor for mineralocorticoid-binding sites and a poor competitor for glucocorticoid-binding sites. The specificity of this molecule was further confirmed by its poor ability to displace [3H]dihydrotestosterone from rat prostate androgenic receptors compared to spironolactone [3-(3-oxo-7 alpha-acetylthio-17 beta-hydroxy-4-androsten-17 alpha-yl) propionic acid gamma-lactone]. In the same experiments, K-prorenoate demonstrated a very low affinity for the two types of receptors. The behavior of [3H]prorenone cytosolic complex was also studied in kidney mince experiments, which showed that the [3H]prorenone complex was not able to translocate into the nucleus. Prorenone inhibited the binding of [3H]aldosterone to the receptor and, consequently, the nuclear binding of aldosterone was not observed.
使用体外系统在大鼠肾脏中研究了两种新的醛固酮拮抗剂，即K-孕烯醇酮[3(17β-羟基-6β,7β-亚甲基-3-氧代-4-雄烯-17α-基)丙酸酯]及其内酯形式的孕烯诺酮[3(17β-羟基-6β,7β-亚甲基-3-氧代-4-雄烯-17α-基)丙酸γ-内酯]。采用最近开发的计算机方法对[3H]孕烯诺酮结合进行的研究表明，存在一类高亲和力、低容量的位点，这些位点似乎是盐皮质激素受体。在针对[3H]醛固酮和[3H]地塞米松结合位点进行的竞争实验中，孕烯诺酮似乎是盐皮质激素结合位点的良好竞争者，而对糖皮质激素结合位点则是较差的竞争者。与螺内酯[3-(3-氧代-7α-乙酰硫基-17β-羟基-4-雄烯-17α-基)丙酸γ-内酯]相比，该分子从大鼠前列腺雄激素受体上置换[3H]双氢睾酮的能力较差，这进一步证实了其特异性。在相同实验中，K-孕烯醇酮对这两种受体的亲和力非常低。还在肾碎块实验中研究了[3H]孕烯诺酮胞质复合物的行为，结果表明[3H]孕烯诺酮复合物无法转运至细胞核。孕烯诺酮抑制[3H]醛固酮与受体的结合，因此未观察到醛固酮的核结合。
