Jean-Baptiste E, Draper M W, Rizack M A
Proc Natl Acad Sci U S A. 1977 Oct;74(10):4329-31. doi: 10.1073/pnas.74.10.4329.
The maximal steroidogenic response (Smax) to adrenocorticotropin (ACTH) is enhanced by the substitution of arginine in position 3. Though the Smax of adrenocorticotropin-(3-10)-octapeptide [ACTH-(3-10)] is only 20% of ACTH-(1-24) in isolated rabbit adrenal cells and 10% in rat cells, [Arg3]ACTH-(3-10) has an Smax comparable to that of the longer peptide. Activity determined from the midpoints of dose-response curves (A50), however, is several orders of magnitude less. The Smax of ACTH-(4-10) is not significantly different from that of the 3-10 analog. Substitution of arginine in the 5 position of ACTH-(4-10) decreases activity for rabbit cells, but does not affect activity for rat cells. The substitution of arginine in the 5 position of ACTH-(1-20) markedly decreases Smax in rabbit but not rat cells. The Smax of [Arg 3,5)]ACTH-(3-10), containing both substitutions, is greater than that of ACTH-(3-10), but much less than that of [Arg3]acth-(3-10) in both species studied. These findings contrast with those in the rabbit adipocyte, where both arginine-containing ACTH analogs have enhanced activity and the effects of both substitutions in a single peptide are additive.
在第3位氨基酸处用精氨酸替代可增强对促肾上腺皮质激素（ACTH）的最大类固醇生成反应（Smax）。尽管促肾上腺皮质激素-（3-10）-八肽[ACTH-（3-10）]的Smax在分离的兔肾上腺细胞中仅为ACTH-（1-24）的20%，在大鼠细胞中为10%，但[Arg3]ACTH-（3-10）的Smax与较长肽段的相当。然而，由剂量反应曲线中点（A50）确定的活性则低几个数量级。ACTH-（4-10）的Smax与3-10类似物的无显著差异。在ACTH-（4-10）的第5位氨基酸处用精氨酸替代会降低兔细胞的活性，但不影响大鼠细胞的活性。在ACTH-（1-20）的第5位氨基酸处用精氨酸替代会显著降低兔细胞而非大鼠细胞的Smax。含有这两种替代的[Arg 3,5)]ACTH-（3-10）的Smax大于ACTH-（3-10）的，但在这两个研究物种中均远低于[Arg3]ACTH-（3-10）的。这些发现与兔脂肪细胞中的情况形成对比，在兔脂肪细胞中，两种含精氨酸的ACTH类似物的活性均增强，且单个肽段中两种替代的效应是相加的。
