This study was designed to examine the effect of calcitonin gene related peptide on gastric acid secretion in the rat. Calcitonin gene related peptide (1 pmol-1 nmol/rat) injected intravenously inhibited basal gastric acid secretion in awake, freely moving rats. Calcitonin gene related peptide decreased gastric secretion stimulated by histamine, pentagastrin, or bethanecol in anaesthetised rats. The inhibitory effect was immediate and most pronounced in the first hour and diminished during the second hour. The N- and C-terminal fragments of calcitonin gene related peptide, CGRP1-14 and [Tyr23]CGRP23-37, did not affect gastric acid secretion. [acetamidomethyl-cys2,7]CGRP, the linear cysteine-protected molecule devoid of the disulphide bridge, was not biologically active. After truncal vagotomy or atropine sulphate, calcitonin gene related peptide did not inhibit gastric secretion. These studies indicate that calcitonin gene related peptide administered peripherally inhibits basal and stimulated gastric acid secretion in the rat. Both C- and N-terminal residues as well as the disulphide bridge are necessary for the inhibitory effect on gastric secretion. Inhibition of gastric acid secretion by calcitonin gene related peptide may depend on intact vagal cholinergic fibres.
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