Benoit R, Bohlen P, Ling N, Esch F, Baird A, Ying S Y, Wehrenberg W B, Guillemin R, Morrison J H, Bakhit C
Adv Exp Med Biol. 1985;188:89-107. doi: 10.1007/978-1-4615-7886-4_6.
The search for a peptide corresponding to the NH2-terminus of somatostatin-28 (SS-28) in tissues has led to the isolation and characterization of somatostatin-28[1-12] from pancreas and hypothalamus. Somatostatin-28[1-12]-like immunoreactivity [SS-28 [1-12]-LI] is widely distributed throughout the central nervous system and the digestive system of rodents and primates, reaching levels comparable to those of somatostatin-14 (SS-14). Antibodies directed against the C-terminal end of the dodecapeptide are more specific and constitute excellent markers for the "prosomatostatin" system in mammalian tissues. In rat brain, SS-28[1-12]-LI material is highly concentrated in nerve fibres and terminals, especially in the median eminence, layer I of neocortex, the outer molecular layer of the dentate gyrus and the striatum. Additionally, immunoreactivity is observed in large multipolar or occasionally pyramidal-like neurons of the neocortex. SS-28[1-12] is secreted from hypothalamus and amygdala by a calcium dependent mechanism. No biological role is presently known for the dodecapeptide. Two other peptides of Mr = 8000 (8 K) and Mr = 5000 (5 K) which contain SS-28[1-12] at their carboxy-termini are present in acid extracts from rat pancreas, brain and spinal cord. These two peptides were isolated from an acid extract of rat brains using ion-exchange chromatography, gel permeation chromatography and reverse-phase HPLC. Results from amino acid analysis and partial sequencing were compared to the sequence of the cDNA encoding rat pre-prosomatostatin (prepro-SS) and revealed that the 8 K peptide is a 76 amino acid molecule corresponding to prepro-SS[25-100] and that the 5K peptide, which contains 44 amino acids, corresponds to prepro-SS [57-100]. The 5 K peptide was generated after cleavage of a Leu-Leu bond at position 56-57 of prepro-SS. The four most predominant peptides of the "prosomatostatin system" presently characterized are: SS-14, SS-28[1-12], SS-28 and prepro-SS[25-100]. Studies on pooled perfusates from rat hypothalamic tissue show that prepro-SS[25-100] is released with SS-28[1-12] in vitro and accounts for 22% of the total SS-28[1-12]-like immunoreactive material released during depolarization. The 5 K peptide is apparently not secreted. The presence of prepro-SS[25-100] in brain implies that, first, prosomatostatin can serve as an immediate precursor for SS-14 without going through SS-28 as an intermediate step and second, other peptides could conceivably be derived from the cryptic portion of the precursor.
在组织中寻找与生长抑素 - 28（SS - 28）氨基末端相对应的肽段，已促使人们从胰腺和下丘脑分离并鉴定出了生长抑素 - 28[1 - 12]。生长抑素 - 28[1 - 12]样免疫反应性物质[SS - 28 [1 - 12] - LI]广泛分布于啮齿动物和灵长类动物的中枢神经系统和消化系统，其水平与生长抑素 - 14（SS - 14）相当。针对该十二肽羧基末端的抗体更具特异性，是哺乳动物组织中“前生长抑素”系统的优良标志物。在大鼠脑中，SS - 28[1 - 12] - LI物质高度集中于神经纤维和终末，尤其是在正中隆起、新皮质第I层、齿状回外分子层和纹状体。此外，在新皮质的大型多极神经元或偶尔的锥体形样神经元中也观察到了免疫反应性。SS - 28[1 - 12]通过钙依赖机制从下丘脑和杏仁核分泌。目前尚不清楚该十二肽的生物学作用。大鼠胰腺、脑和脊髓的酸提取物中存在另外两种羧基末端含有SS - 28[1 - 12]的肽，其相对分子质量分别为8000（8K）和5000（5K）。使用离子交换色谱、凝胶渗透色谱和反相高效液相色谱从大鼠脑的酸提取物中分离出了这两种肽。将氨基酸分析和部分测序结果与编码大鼠前生长抑素原（前pro - SS）的cDNA序列进行比较，结果显示8K肽是一个76个氨基酸的分子，对应于前pro - SS[25 - 100]，而含有44个氨基酸的5K肽对应于前pro - SS [57 - 100]。5K肽是在前pro - SS第56 - 57位的Leu - Leu键断裂后产生的。目前已鉴定出的“前生长抑素系统”中四种最主要的肽为：SS - 14、SS - 28[1 - 12]、SS - 28和前pro - SS[25 - 100]。对大鼠下丘脑组织混合灌流液的研究表明，前pro - SS[25 - 100]在体外与SS - 28[1 - 12]一起释放，占去极化过程中释放的总SS - 28[1 - 12]样免疫反应性物质的22%。5K肽显然不分泌。脑中存在前pro - SS[25 - 100]意味着，首先，前生长抑素可以作为SS - 14的直接前体，而无需以SS - 28作为中间步骤；其次，可以想象其他肽可能源自该前体的隐蔽部分。
