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GRP and stimulation of acid secretion
  1. H L Waldum1,
  2. A K Sandvik2
  1. 1Norwegian University of Science and Technology, Department of Intra-abdominal Diseases, University Hospital of Trondheim, N-7006 Trondheim, Norway; helge.waldum{at}
  2. 2Norwegian University of Science and Technology, Department of Physiology and Biomedical Engineering, University Hospital of Trondheim, N-7006 Trondheim, Norway;{at}
  1. P Hildebrand3,
  2. C Beglinger3
  1. 3Department of Research and Division of Gastroenterology, University Hospital, CH-4031 Basel, Switzerland

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We read with interest the article by Hildebrand et al on the effect of gastrin releasing peptide (GRP) on acid secretion in healthy individuals (Gut 2001;49:23–8). This study shows that a GRP antagonist (BIM 26226) inhibits acid secretion with no effect on plasma gastrin. The authors concluded that GRP stimulated acid secretion by a non-gastrin mechanism. Their results are in agreement with previous studies from our laboratory which indicate that GRP in the rat stimulates acid secretion by a mechanism other than by gastrin release.1 We also found that GRP releases somatostatin and inhibits histamine release from the oxyntic mucosa, an effect which viewed in isolation should counteract acid secretory stimulation.1

These studies and others demonstrate the complexity of neuropeptide mechanisms in the regulation of gastric acid secretion. In our opinion, great care should be shown when interpreting the results from experiments using neuropeptides in the study of gastric physiology and pharmacology.


Authors' reply

Our conclusion that gastrin releasing peptide (GRP) is not a physiological regulator of gastrin secretion in humans stands against an impressive body of evidence collected in the past 30 years in different animal species. Even in humans, several lines of evidence would support a role for GRP as a regulator of the G cell: infusion of exogenous GRP stimulates gastrin release in humans but GRP also releases gastrin from isolated human g cells in vitro.1–,3 In several laboratory animals, GRP antagonists or GRP antibodies inhibit the release of gastrin to a variety of stimulants.4,5 Our results obtained in healthy male subjects could therefore be due to species differences with respect to the physiological role of GRP as a gastrin secretagogue. As pointed out by Waldum and Sandvik, some studies in rats have also shown that GRP can stimulate acid secretion independent of gastrin release. Along the same lines, gastrin concentrations are normal in mice lacking the GRP receptor.6 As gastrin secretion is regulated by various factors, including nutrients, G cell responses to GRP reflect the balance of direct stimulatory effects and indirect inhibitory factors. We hope that our data will generate new interest in studying the role of this interesting peptide in regulating gastrointestinal functions.


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