Rehfeld J F
Am J Physiol. 1981 Apr;240(4):G255-66. doi: 10.1152/ajpgi.1981.240.4.G255.
The gastrointestinal peptide hormones, gastrin and cholecystokinin (CCK), display four molecular characteristics. 1) Homology. Sequences of the primary structures are identical. Because the identity comprises the active site, the homology is functionally important. The homology reflects evolution from a common ancestor. 2) Heterogeneity. Each hormone exists in different molecular forms in any single species. The heterogeneity comprises both variations in lengths of the polypeptide backbone, "macroheterogeneity," and derivatizations of single amino acid residues, "microheterogeneity." Both types of modification govern the biological potency. The heterogeneity reflects enzymatic modifications of the primary ribosomal translation product. 3) Ubiquity. Each hormone is synthetized in different cell types, which are localized in gastrointestinal as well as extra-gastrointestinal tissues. The cell type determines the route by which the active peptide(s) reaches its target, either via blood (endocrine secretion) or by local release (neurocrine and paracrine secretion). Inasmuch as all cells contain gastrin and CCK genes, the variable expression probably reflects differentiation in development of the posttranscriptional biosynthetic machinery. 4) Differential principality. In different tissues and cells, different molecular forms may predominate. Moreover, one form is more potent with respect to one effect (e.g., CCK-8 in relation to pancreatic exocrine secretion), whereas another form (CCK-4) is more potent with respect to another effect (pancreatic endocrine secretion). Together the differential principality and secretory routes (blood borne or local) ensure that gastrin and CCK peptides regulate their targets with optimal effect in spite of the heterogeneity and wide distribution, which otherwise might cause disturbing interactions and subsequent inefficacy. The key to a better understanding of the basis characteristics is knowledge about the evolution and expression of the structural gene(s) for gastrin and CCK. Acquisition of such knowledge will be of considerable value, since available evidence suggests that the gastrin-CCK system is a good model for general features of regulatory peptides.
胃肠肽激素，即胃泌素和胆囊收缩素（CCK），具有四个分子特征。1）同源性。一级结构序列相同。由于这种相同性包含活性位点，所以同源性在功能上很重要。同源性反映了共同祖先的进化。2）异质性。每种激素在任何单一物种中都以不同的分子形式存在。异质性包括多肽主链长度的变化，即“宏观异质性”，以及单个氨基酸残基的衍生化，即“微观异质性”。这两种修饰类型都决定了生物活性。异质性反映了核糖体初级翻译产物的酶促修饰。3）普遍性。每种激素在不同的细胞类型中合成，这些细胞位于胃肠道以及胃肠道外组织中。细胞类型决定了活性肽到达其靶标的途径，要么通过血液（内分泌分泌），要么通过局部释放（神经分泌和旁分泌分泌）。由于所有细胞都含有胃泌素和CCK基因，这种可变表达可能反映了转录后生物合成机制发育过程中的分化。4）差异主导性。在不同的组织和细胞中，不同的分子形式可能占主导地位。此外，一种形式对一种效应（例如，CCK - 8对胰腺外分泌）更有效，而另一种形式（CCK - 4）对另一种效应（胰腺内分泌分泌）更有效。差异主导性和分泌途径（血液传播或局部）共同确保胃泌素和CCK肽尽管存在异质性和广泛分布，但仍能以最佳效果调节其靶标，否则可能会导致干扰性相互作用和随后的无效性。更好地理解这些基本特征的关键在于了解胃泌素和CCK结构基因的进化和表达。获得这些知识将具有相当大的价值，因为现有证据表明胃泌素 - CCK系统是调节肽一般特征的良好模型。
