Morris H R, Panico M, Etienne T, Tippins J, Girgis S I, MacIntyre I
Nature. 1984;308(5961):746-8. doi: 10.1038/308746a0.
The rat calcitonin gene has recently been shown to encode a novel peptide (rat calcitonin gene-related peptide, rCGRP) thought to be produced in nervous tissue after tissue-specific RNA processing. This peptide has so far been identified only in rat tissue, by immunocytochemistry and immunoassay. We now report the isolation of a related (89% homology) peptide from human tissue (hCGRP) which we have sequenced using a novel mass spectrometric approach, fast atom bombardment (FAB) mapping. The human peptide differs significantly from the predicted rCGRP structure in four positions in the amino acid sequence (three effecting charge changes), and the presence of a disulphide bridge and an amide, surmised in the rat work, is proven in the hCGRP molecule. hCGRP was present in plasma from 10 patients with medullary thyroid carcinoma (MTC) and in 6 MTC tumours removed at surgery, suggesting the tissue distribution may differ from that in the rat where the peptide is reported to be absent from thyroid tissue. hCGRP is shown to have biological activity and it is possible that its presence in MTC plasma may be responsible for some of the symptoms in this disease.
最近研究表明，大鼠降钙素基因编码一种新的肽（大鼠降钙素基因相关肽，rCGRP），该肽被认为是在组织特异性RNA加工后于神经组织中产生的。迄今为止，仅通过免疫细胞化学和免疫测定在大鼠组织中鉴定出了这种肽。我们现在报告从人组织中分离出一种相关肽（同源性89%）（hCGRP），我们使用一种新型质谱方法——快原子轰击（FAB）图谱法对其进行了测序。人肽在氨基酸序列的四个位置上与预测的rCGRP结构有显著差异（三个导致电荷变化），并且在大鼠研究中推测存在的二硫键和酰胺在hCGRP分子中得到了证实。hCGRP存在于10例甲状腺髓样癌（MTC）患者的血浆中以及6例手术切除的MTC肿瘤中，这表明其组织分布可能与大鼠不同，据报道大鼠甲状腺组织中不存在这种肽。研究表明hCGRP具有生物活性，其在MTC血浆中的存在可能是该疾病某些症状的原因。
