Deghenghi R, Papotti M, Ghigo E, Muccioli G
Europeptides, Argenteuil, France.
J Endocrinol Invest. 2001 Jan;24(1):RC1-3. doi: 10.1007/BF03343800.
Antagonism between GH secretagogues (GHS) and somatostatin (SRIH) has been postulated and demonstrated, but SRIH does not bind to GHS receptors (GHS-R) and potent synthetic peptidyl GHS (GHRP6, hexarelin) do not displace radiolabeled SRIH from its receptors. However, non-natural SRIH octapeptide agonists (mainly lanreotide and vapreotide) displace 125I-Tyr-Ala-hexarelin from pituitary binding sites suggesting that an endogenous factor related to SRIH might exist and interact with GHS-R. Our aims were to investigate the ability of different SRIH-like peptides such as various SRIH fragments (SRIH 3-14, SRIH 7-14, SRIH 3-10, SRIH 7-10, SRIH 2-9) and a natural neuropeptide that shows a high structural homology with SRIH such as cortistatin-14 (CST) to compete with 125I-Tyr-Ala-hexarelin for human pituitary binding sites and to compare their binding affinity with that of hexarelin and ghrelin, a gastric-derived peptidyl GHS that has been proposed as a natural ligand of GHS-R. While the binding of 125I-Tyr-Ala-hexarelin to pituitary membranes was completely displaced by unlabelled hexarelin, ghrelin and CST, none of the SRIH fragments tested inhibited this binding. Ghrelin and CST exhibited a similar affinity (4.6-5.4 x 10(-7) mol/l) for the binding while hexarelin was more effective by about four orders of magnitude in displacing 125I-Tyr-Ala-hexarelin. Our data demonstrate for the first time that cortistatin, a natural peptide related to SRIH, binds to GHS-R and suggest that this factor may play a role in modulating the activity of these receptors.
生长激素促分泌素（GHS）与生长抑素（SRIH）之间的拮抗作用已被提出并得到证实，但SRIH不与GHS受体（GHS-R）结合，且强效合成肽基GHS（GHRP6、六肽生长激素释放肽）不能从其受体上取代放射性标记的SRIH。然而，非天然的SRIH八肽激动剂（主要是兰瑞肽和伐普肽）能从垂体结合位点取代125I-Tyr-Ala-六肽生长激素释放肽，这表明可能存在一种与SRIH相关的内源性因子并与GHS-R相互作用。我们的目的是研究不同的SRIH样肽，如各种SRIH片段（SRIH 3-14、SRIH 7-14、SRIH 3-10、SRIH 7-10、SRIH 2-9）以及一种与SRIH具有高度结构同源性的天然神经肽，如可体松抑制素-14（CST），与125I-Tyr-Ala-六肽生长激素释放肽竞争人垂体结合位点的能力，并将它们的结合亲和力与六肽生长激素释放肽和胃源肽基GHS胃饥饿素（已被认为是GHS-R的天然配体）的结合亲和力进行比较。虽然未标记的六肽生长激素释放肽、胃饥饿素和CST能完全取代125I-Tyr-Ala-六肽生长激素释放肽与垂体膜的结合，但所测试的SRIH片段均未抑制这种结合。胃饥饿素和CST对这种结合表现出相似的亲和力（4.6 - 5.4×10(-7) mol/l），而六肽生长激素释放在取代125I-Tyr-Ala-六肽生长激素释放肽方面的效果要强约四个数量级。我们的数据首次证明，与SRIH相关的天然肽可体松抑制素能与GHS-R结合，并表明该因子可能在调节这些受体的活性中发挥作用。
