Infusion of a novel peptide, calcitonin gene-related peptide (CGRP) in man. Pharmacokinetics and effects on gastric acid secretion and on gastrointestinal hormones.
Calcitonin gene-related peptide (CGRP) is a recently discovered widespread regulatory peptide which is encoded in the same gene as calcitonin. We assessed 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. To assess its pharmacokinetic parameters in man the MCR 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 less than 0.01 and -40% of basal, P less than 0.005, respectively). There was a significant fall in basal levels of gastrin (-39%, P less than 0.001); gastric inhibitory peptide (-44.7%, P less than 0.001); enteroglucagon (-25%, P less than 0.001) and neurotensin (-33%, P less than 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.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005755:Gastrins / Q000097:blood; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D009037:Motilin / Q000097:blood; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology*; D009496:Neurotensin / Q000097:blood; D010191:Pancreatic Polypeptide / Q000097:blood; D010434:Pepsin A / Q000378:metabolism; D011674:Pulse / Q000187:drug effects; D011863:Radioimmunoassay
D001786:Blood Glucose; D005755:Gastrins; D005768:Gastrointestinal Hormones; D007328:Insulin; D009419:Nerve Tissue Proteins; D009496:Neurotensin; D009037:Motilin; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide; D005934:Glucagon; D010434:Pepsin A; D015740:Calcitonin Gene-Related Peptide