Meyers C A, Coy D H, Murphy W A, Redding T W, Arimura A, Schally A V
Proc Natl Acad Sci U S A. 1980 Jan;77(1):577-9. doi: 10.1073/pnas.77.1.577.
[Phe4]Somatostatin was twice as active as somatostatin (SS) in suppressing rat growth hormone release in vitro but had only weak activity toward inhibition of insulin and glucagon release in vivo. The ability of this analogue to inhibit growth hormone release more actively than SS was confirmed in vivo by two separately designed bioassays. Further structure/activity studies of position 4 were carried out with [Glu4]SS, [Thr4]SS, and des-Lys4-SS, all of which had negligible inhibiting activity in the pituitary and pancreas. In this context the strikingly selective activity of [Phe4]SS suggests a fundamental difference in the SS receptors of pituitary and pancreas and the normal side-chain basicity of position 4 appears to be more important for action in pancreas than in pituitary. [Phe4]SS has properties that may be useful in the development of agents for the treatment of acromegaly or other disorders associated with increased growth hormone levels.
[苯丙氨酸4]生长抑素在体外抑制大鼠生长激素释放方面的活性是生长抑素（SS）的两倍，但在体内对抑制胰岛素和胰高血糖素释放的活性较弱。这种类似物比SS更能有效抑制生长激素释放的能力在体内通过两种独立设计的生物测定得到了证实。用[谷氨酸4]SS、[苏氨酸4]SS和去赖氨酸4-SS对第4位进行了进一步的结构/活性研究，所有这些在垂体和胰腺中均具有可忽略不计的抑制活性。在这种情况下，[苯丙氨酸4]SS显著的选择性活性表明垂体和胰腺的生长抑素受体存在根本差异，并且第4位正常的侧链碱性对于在胰腺中的作用似乎比在垂体中更重要。[苯丙氨酸4]生长抑素具有的特性可能有助于开发用于治疗肢端肥大症或其他与生长激素水平升高相关疾病的药物。
