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Effect of CGRP antagonist, alpha-CGRP 8-37, on acid secretion in the dog

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Abstract

The recently synthesized calcitonin gene-related peptide (CGRP) antagonist, human alpha-CGRP 8-37, was used to study its effects on gastric acid secretion. Four dogs with gastric fistula were used to measure the antagonist's physiologic effects in the stomach. All dogs received a bactopeptone dextrose meal (intragastric titration to pH 5.5) with either continuous CGRP 8-37 (1000 pmol/kg/hr) or saline (control). Additionally, intravenous bombesin (75–600 ng/kg/hr) and bethanecol (12.5–100 µg/kg/hr) was tested in the presence of the antagonist. Plasma gastrin levels also were measured via radioimmunoassay (RIA) in control and CGRP 8-37-stimulated animals. Gastric acid secretion increased by 100% with infusion of 1000 pmol/kg/hr CGRP 8-37 when compared to the control. Acid output increased 98% with both intravenous antagonist and 600 ng/kg/hr bombesin when compared to bombesin alone. However, no augmentation of acid secretion by CGRP 8-37 was shown with 25 µg/kg/hr bethanecol. RIA of plasma gastrin demonstrated no effect with the antagonist when given alone and did not increase bombesin-stimulated gastrin release. We conclude that CGRP 8-37 blocks native CGRP inhibitory effects on gastric acid secretion. Our findings of potentiation of acid secretion by bombesin as well as no change in gastrin levels in the presence of the antagonist is likely due to a blockage in a noncholinergic neuron to the somatostatin cell. Furthermore, CGRP 8-37 did not increase bethanecolstimulated acid secretion, most likely due to bethanecol's (acetylcholine) nearly ubiquitous positive effects on acid secretion.

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Authors and Affiliations

  1. From the Department of Surgery, Durham, VA

    D. Curtis Lawson MS, Christopher R. Mantyh MD & Theodore N. Pappas MD

  2. Duke University Medical Center, Box 3479, 27710, Durham, North Carolina

    D. Curtis Lawson MS, Christopher R. Mantyh MD & Theodore N. Pappas MD

Authors
  1. D. Curtis Lawson MS
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  2. Christopher R. Mantyh MD
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  3. Theodore N. Pappas MD
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Funded by NIH Grant DK 40790.

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Curtis Lawson, D., Mantyh, C.R. & Pappas, T.N. Effect of CGRP antagonist, alpha-CGRP 8-37, on acid secretion in the dog. Digest Dis Sci 39, 1405–1408 (1994). https://doi.org/10.1007/BF02088041

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  • DOI: https://doi.org/10.1007/BF02088041

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