Pressor and cardioaccelerator effects of gamma MSH and related peptides.
Pressor and cardioaccelerator effects of gamma MSH and related peptides.
复制标题
γ MSH 和相关肽的升压和心脏加速作用。
DOI：
10.1016/0024-3205(85)90197-3
复制
发表时间：
1985
期刊：
影响因子：
6.1
通讯作者：
Gruber,KA
中科院分区：
文献类型：
--
作者：
Klein,MC;Hutchins,PM;Lymangrover,JR;Gruber,KA
我们最近证实，ACTH 1 - 39的高血压和利钠作用可以在ACTH的非类固醇生成片段ACTH 4 -10中发现。ACTH或ACTH 4 - 10的这些作用可能是由于它们作为γMSH的弱激动剂的能力。γMSH位于阿片皮质素原（pro-opiocortin）的16 K N端，含有与ACTH 4 -10、γ MSH 3 - 9类似的序列。结果表明，γ MSH 3 -9与ACTH 4 -10具有基本相同的活性。在γ MSH 3 -9（γ 2 MSH）上增加5个氨基酸残基，可显著增强升压和心脏加速活性。通过对ACTH 4 - 10序列进行空间限制，用D-Phe取代#7位的L-Phe残基，或通过半Cys 4，半Cys 10分子内二硫桥衍生化使肽环化，导致心血管活性增加。和γ 2 MSH是由于反向旋转三维结构的假设。γ 2 MSH中的额外残基似乎特异性增强γ MSH 3 -9的心血管活性。结果表明，存在一类新的垂体肽与心血管活动，这需要一个定义的三维结构的假设。
We have recently demonstrated that the hypertensiongenic and natriuretic actions of ACTH1–39can be found in a non-steroidogenic fragment of ACTH, ACTH4–10. These effects of ACTH or ACTH4–10may be due to their ability to act as weak agonists of γMSH. γMSH is found in the 16K N-terminus of pro-opiocortin, and contains a sequence analogous to ACTH4–10, γMSH3–9.We investigated the cardiovascular effects of γ2MSH, γMSH3–9, and sterically restricted analogs of ACTH4–10. The results indicate that γMSH3–9, had essentially the same activities as ACTH4–10. The addition of five other amino acid residues to γMSH3–9(γ2MSH) resulted in significant enhancement of pressor and cardioaccelerator activity. Steric restriction of the ACTH4–10sequence by the substitution of a D-Phe in place of an L-Phe residue in position #7, or cyclization of the peptide by a half-Cys4, half Cys10intramolecular disulfide-bridge derivatization, resulted in increased cardiovascular activities.Based on these data, the cardiovascular actions of ACTH4–10, γMSH3–9, and γ2MSH are predicted to be due to the assumption of a reverse-turn three-dimensional structure. The additional residues in γ2MSH appear to specifically enhance the cardiovascular activities of γMSH3–9. The results suggest the existence of a new class of hypophyseal peptides with cardiovascular activities, which require the assumption of a defined three-dimensional structure.