Adrenomedullin, amylin, calcitonin gene-related peptide and their fragments are potent inhibitors of gastric acid secretion in rats.

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.