Calcitonin gene-related peptides I and II and calcitonin: Distinct effects on gastric acid secretion in humans

The human calcitonin gene-related peptides I and II (CGRP I and CGRP II) are two neuropeptides that have been recognized throughout the gastrointestinal system including the stomach. The present study was undertaken to compare in healthy volunteers the effects of intravenous infusions of CGRP I and CGRP II (79 pmol/kg · h) on pentagastrinstimulated acid secretion to those of calcitonin (88 pmol/kg · h). Calcitonin gene-related peptide I did not inhibit basal or pentagastrin-stimulated acid secretion. However, CGRP II and calcitonin inhibited pentagastrin-stimulated acid responses by 20% and 28%, respectively (p < 0.05 and p < 0.01), whereas basal acid output was only reduced with calcitonin (p < 0.05). These effects were recognized with low doses of pentagastrin, and absent with high doses suggesting competitive inhibition. Furthermore, step-doses of CGRP I and CGRP II (79–320 pmol/kg · h) were given intravenously on continuous pentagastrin stimulation and compared with calcitonin (88–352 pmol/kg h). Calcitonin gene-related peptide II and calcitonin induced a dose-dependent decrease of acid output, whereas CGRP I was ineffective. The inhibitory effects of CGRP II and calcitonin are not due to increased gastric alkaline secretion or to somatostatin release, as neither peptide stimulated gastric bicarbonate secretion or induced an increase in circulating somatostatin. In conclusion, CGRP II, unlike CGRP I, inhibits gastric acid secretion in humans. Inhibitory effects of CGRP II and of calcitonin were comparable. The results imply that CGRP I and II, at the level of the stomach, have distinct biological properties in humans.