Rossowski W J, Jiang N Y, Coy D H
Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA.
Eur J Pharmacol. 1997 Oct 1;336(1):51-63. doi: 10.1016/s0014-2999(97)01252-1.
Adrenomedullin, amylin and calcitonin gene-related peptides (CGRP) share close sequence homology and have overlapping spectra of biological activities, particularly with respect to cardiovascular and gastrointestinal functions. Comparisons of the effects of these three peptides on gastric acid release have been made by i.v. infusions in conscious rats equipped with gastric fistulae. All peptides were extremely potent inhibitors of basal, pentagastrin- and 2-deoxy-D-glucose-stimulated gastric acid secretion with IC50 values in the subnanomolar to nanomolar range. These effects were not inhibited by C-terminal extra-cyclic fragments of the peptides which often act as competitive receptor antagonists in other biological systems. At high concentrations C-terminal fragments of human adrenomedullin and rat alpha-calcitonin gene-related peptide displayed some receptor agonist activity. Furthermore, the N-terminally situated disulfide-bridged ring fragments, human adrenomedullin-(15-22), rat amylin-(1-8) and rat alpha-calcitonin gene-related peptide-(1-8), retained significant gastric acid inhibitory potencies thus suggesting involvement of receptor(s) with significantly differing ligand binding profiles than those characterized previously.
肾上腺髓质素、胰淀素和降钙素基因相关肽（CGRP）具有相似的序列同源性，且生物活性谱存在重叠，尤其是在心血管和胃肠功能方面。通过对装有胃瘘的清醒大鼠进行静脉输注，比较了这三种肽对胃酸分泌的影响。所有肽都是基础胃酸分泌、五肽胃泌素和2-脱氧-D-葡萄糖刺激的胃酸分泌的强效抑制剂，IC50值在亚纳摩尔至纳摩尔范围内。这些肽的C末端外环片段在其他生物系统中常作为竞争性受体拮抗剂，但并未抑制这些作用。在高浓度下，人肾上腺髓质素和大鼠α-降钙素基因相关肽的C末端片段表现出一些受体激动剂活性。此外，位于N末端的二硫键桥连环片段，人肾上腺髓质素-（15-22）、大鼠胰淀素-（1-8）和大鼠α-降钙素基因相关肽-（1-8），仍具有显著的胃酸抑制效力，因此表明存在与先前表征的受体具有明显不同配体结合特征的受体。
