ADRENOMEDULLIN, AMYLIN, CALCITONIN-GENE-RELATED PEPTIDE AND THEIR FRAGMENTS ARE POTENT INHIBITORS OF GASTRIC-ACID SECRETION IN RATS

Adrenomedullin, amylin and calcitonin related peptides (CGRP) share cl ose sequence homology and have overlapping spectra of biological activ ities, particularly with respect to cardiovascular and gastrointestina l functions. Comparisons of the effects of-these three peptides on gas tric acid release have been made by i.v. infusions in conscious rats e quipped with gastric fistulae. All peptides were extremely potent inhi bitors of basal, pentagastrin-and 2-deoxy-D-glucose-stimulated gastric acid secretion with IC,, values in the subnanomolar to nanomolar rang e. These effects were not inhibited by C-terminal extra-cyclic fragmen ts of the peptides which often act as competitive receptor antagonists in other biological systems. At high concentrations C-terminal fragme nts of human adrenomedullin and rat alpha-calcitonin gene-related pept ide displayed some receptor agonist activity. Furthermore, the N-termi nally situated disulfide-bridged ring fragments, human adrenomedullin- (15-22), rat amylin-(1-8) and rat alpha-calcitonin gene-related peptid e-(1-8), retained significant gastric acid inhibitory potencies thus s uggesting involvement of receptor(s) with significantly differing liga nd binding profiles than those characterized previously. (C) 1997 Else vier Science B.V.