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Infusion of a novel peptide calcitonin gene related peptide in man pharmacokinetics and effects on gastric acid secretion and on gastrointestinal hormones



Infusion of a novel peptide calcitonin gene related peptide in man pharmacokinetics and effects on gastric acid secretion and on gastrointestinal hormones



Regulatory Peptides 10(2-3): 189-198



Calcitonin gene-related peptide (CGRP) is a recently discovered widespread regulatory peptide which is encoded in the same gene as calcitonin. The effect of systemic infusion of synthetic rat CGRP at low dose (range 0.32-2.56 pmol/kg per min) on submaximal pentagastrin-stimulated gastric secretion and on gastrointestinal hormones was assessed. To assess its pharmacokinetic parameters in man the MCR [metabolic clearance rate] and plasma half-life were estimated by the continuous infusion method. Gastric acid output and pepsin secretion were significantly reduced by CGRP (-29% of basal, P < 0.01 and -40% of basal, P < 0.005, respectively). There was a significant fall in basal levels of gastrin (-39%, P < 0.001); gastric inhibitory peptide (-44.7%, P < 0.001); enteroglucagon (-25%, P < 0.001) and neurotensin (-33%, P < 0.05). There was no significant change in plasma levels of insulin, motilin, pancreatic polypeptide or glucose. Suppression of gastric secretion and the fall in gastrointestinal hormones was prolonged and basal levels were not re-established after stopping the CGRP infusion. The disappearance curve of immunoreactive CGRP from the plasma was bi-exponential. The plasma half-life of immunoreactive CGRP was calculated as 6.9 .+-. 0.9 min for the fast decay and 26.4 .+-. 4.7 min for the slow decay. The calculated MCR was 11.3 .+-. 1.2 ml/kg per min. Except for flushing of the face no untoward effects were observed. The results of this study suggest the possibility that CGRP could play a role in the regulation of gastric secretion and gastrointestinal hormone release.

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