CGRP antagonists enhance gastric acid secretion in 2-h pylorus-ligated rats

The influence of calcitonin gene-related peptide (CGRP) antagonists on gastric acid secretion was investigated in rats. Intravenous injection of the CGRP receptor antagonist, CGRP(8-37) (128 nmol/kg) or the CGRP antibody #4901 (4.8 mg/kg, IV) completely prevented alpha-CGRP (3.9 nmol/kg/h)-induced inhibition of acid response to pentagastrin in urethane-anesthetized rats with gastric fistula. CGRP antibody (4.8 mg/kg, IV) increased by 93% gastric acid secretion in conscious rats with pylorus ligation for 2 h. (CGRP(8-73) (128 nmol/kg, IV) also enhanced the acid response measured 2 h after pylorus ligation in conscious rats and in urethane-anesthetized rats infused with pentagastrin by 91% and 56%, respectively. These results suggest that endogenous CGRP attenuates the gastric acid response measured 2 h after pylorus ligation.