de Lecea L, Ruiz-Lozano P, Danielson P E, Peelle-Kirley J, Foye P E, Frankel W N, Sutcliffe J G
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Genomics. 1997 Jun 15;42(3):499-506. doi: 10.1006/geno.1997.4763.
Cortistatin is a 14-residue putative neuropeptide with strong structural similarity to somatostatin and is expressed predominantly in cortical GABAergic interneurons of rats. Administration of cortistatin into the brain ventricles specifically enhances slow-wave sleep, presumably by antagonizing the effects of acetylcholine on cortical excitability. Here we report the identification of cDNAs corresponding to mouse and human preprocortistatin and the mRNA distribution and gene mapping of mouse cortistatin. Analysis of the nucleotide and predicted amino acid sequences from rat and mouse reveals that the 14 C-terminal residues of preprocortistatin, which make up the sequence that is most similar to somatostatin, are conserved between species. Lack of conservation of other dibasic amino acid residues whose cleavage by prohormone convertases would give rise to additional peptides suggests that cortistatin-14 is the only active peptide derived from the precursor. As in the rat, mouse preprocortistatin mRNA is present in GABAergic interneurons in the cerebral cortex and hippocampus. The preprocortistatin gene maps to mouse chromosome 4, in a region showing conserved synteny with human 1p36. The human putative cortistatin peptide has an arginine for lysine substitution, compared to the rat and mouse products, and is N-terminally extended by 3 amino acids.
促皮质素抑制素是一种由14个氨基酸残基组成的假定神经肽，与生长抑素具有很强的结构相似性，主要在大鼠的皮质GABA能中间神经元中表达。向脑室注射促皮质素抑制素可特异性增强慢波睡眠，推测是通过拮抗乙酰胆碱对皮质兴奋性的影响来实现的。在此，我们报告了与小鼠和人类前促皮质素抑制素对应的cDNA的鉴定以及小鼠促皮质素抑制素的mRNA分布和基因定位。对大鼠和小鼠的核苷酸序列及预测的氨基酸序列分析表明，前促皮质素抑制素的14个C末端残基构成了与生长抑素最相似的序列，在不同物种间是保守的。其他双碱性氨基酸残基缺乏保守性，其被激素原转化酶切割会产生额外的肽段，这表明促皮质素抑制素-14是从前体衍生出的唯一活性肽。与大鼠一样，小鼠前促皮质素抑制素mRNA存在于大脑皮质和海马体的GABA能中间神经元中。前促皮质素抑制素基因定位于小鼠4号染色体上，该区域与人1p36显示出保守的同线性。与大鼠和小鼠的产物相比，人类假定的促皮质素抑制素肽有一个赖氨酸被精氨酸取代的情况，并且在N末端延伸了3个氨基酸。
