Skip to main content

Advertisement

Log in

Comparison of the actions of acylated and desacylated ghrelin on acid secretion in the rat stomach

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Ghrelin, a growth-hormone-releasing peptide, has two major molecular forms: acylated (acyl) and desacylated (desacyl). Recent studies suggest different roles for these two forms. In the present study, we compared desacyl and acyl ghrelin with regard to acid secretion and histamine production in the rat stomach.

Methods

We performed in vivo experiments using gastric lumen-perfused rats. The effects of the two forms of ghrelin on gastrin (gastrin-17)-stimulated acid secretion were also examined. Furthermore, to examine the effects of ghrelin on histamine production, histidine decarboxylase messenger ribonucleic acid in the gastric corpus mucosa was measured by reverse transcription-polymerase chain reaction.

Results

Intravenous administration of acyl ghrelin at 20 μg/kg increased gastric acid secretion to 4.8 times greater than control levels. However, desacyl ghrelin had no effect on acid secretion, even at 200 μg/kg. Acyl ghrelin enhanced gastrin-stimulated acid secretion while desacyl ghrelin did not. Vagotomy markedly inhibited the enhancement of gastrin-stimulated acid secretion by acyl ghrelin. Acyl ghrelin increased histidine decarboxylase messenger ribonucleic acid concentration by 2.3 times compared with basal levels at 1 h after administration and by 2.7 times at 2 h after administration; desacyl ghrelin had no such effect. Synergism between acyl ghrelin and gastrin was seen regarding histidine decarboxylase messenger ribonucleic acid concentration.

Conclusions

The results indicate that acyl ghrelin stimulates gastric acid secretion via a mechanism involving activation of the vagus nerve and histamine release and synthesis and that desacyl ghrelin has no action on gastric acid secretion. Furthermore, the results demonstrate synergism between gastrin and acyl ghrelin in terms of gastric acid secretion via a mechanism involving histamine release and synthesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a novel growth hormone releasing acylated peptide from stomach. Nature. 1999;402:656–60.

    Article  CAS  PubMed  Google Scholar 

  2. Date Y, Kojima Y, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, et al. Ghrelin a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000;141:4255–61.

    Article  CAS  PubMed  Google Scholar 

  3. Tscop M, Smiley DL, Heiman M. Ghrelin induces adiposity in rodents. Nature. 2000;407:908–13.

    Article  Google Scholar 

  4. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141:4325–8.

    Article  CAS  PubMed  Google Scholar 

  5. Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I. Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression. Endocrinology. 2000;141:4797–800.

    Article  CAS  PubMed  Google Scholar 

  6. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194–8.

    Article  CAS  PubMed  Google Scholar 

  7. Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 2001;120:337–45.

    Article  CAS  PubMed  Google Scholar 

  8. Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes. 2001;50:227–32.

    Article  CAS  PubMed  Google Scholar 

  9. Wren AM, Seal LA, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992–5.

    Article  CAS  PubMed  Google Scholar 

  10. Masuda Y, Tanaka T, Inomata M, Ohnuma N, Tanaka S, Itoh Z, et al. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun. 2000;276:905–8.

    Article  CAS  PubMed  Google Scholar 

  11. Date Y, Nakazato M, Murakami N, Kojima M, Kangawa K, Matsukura S. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem Biophys Res Commun. 2001;280:904–7.

    Article  CAS  PubMed  Google Scholar 

  12. Yakabi K, Shoki R, Onouchi T, Tanaka T, Ohno S, Miura S, et al. Histamine mediates the stimulatory action of ghrelin on acid secretion in rat stomach. Dig Dis Sci. 2006;56:1313–21.

    Article  Google Scholar 

  13. Hosoda H, Kojima M, Matsuo H, Kangawa K. Ghrelin and desacyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun. 2000;279:909–13.

    Article  CAS  PubMed  Google Scholar 

  14. Kojima M, Hosoda H, Matsuo H, Kangawa K. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab. 2001;12:118–22.

    Article  CAS  PubMed  Google Scholar 

  15. Broglio F, Benso A, Gottero C, Prodam F, Gauna C, Filtri L, et al. Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans. J Endocrinol Invest. 2003;26:192–6.

    CAS  PubMed  Google Scholar 

  16. Yoshimoto A, Mori K, Sugawara A, Mukoyama M, Yahata K, Suganami T, et al. Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J Am Soc Nephrol. 2002;13:2748–52.

    Article  CAS  PubMed  Google Scholar 

  17. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni FS, Fubini F, et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol. 2002;159:1029–37.

    Article  CAS  PubMed  Google Scholar 

  18. Bedendi I, Alloatti G, Marcantoni A, Malan D, Catapano F, Ghè C, et al. Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin. Eur J Pharmacol. 2003;476:87–95.

    Article  CAS  PubMed  Google Scholar 

  19. Cassoni P, Pappoti M, Ghè C, Catapano F, Sapino A, Craziani A, et al. Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab. 2001;86:1738–45.

    Article  CAS  PubMed  Google Scholar 

  20. Asakawa A, Inui A, Fujimiya M, Sakamaki R, Shinfuku N, Ueta Y, et al. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut. 2005;54:18–24.

    Article  CAS  PubMed  Google Scholar 

  21. Fukumoto K, Nakahara K, Katayama T, Miyazatao M, Kangawa K, Murakami N. Synergistic action of ghrelin on gastric acid secretion in rats. Biochem Biophys Res Commun. 2008;374:60–3.

    Article  CAS  PubMed  Google Scholar 

  22. Yakabi K, Mimura H, Iwabuchi H, Ro S, Nakamura T. Interleukin-8 enhances tetra-gastrin-stimulated acid secretion in vivo. Dig Dis Sci. 1998;43:2317–21.

    Article  CAS  PubMed  Google Scholar 

  23. Kreuzer KA, Lass U, Bohn A, Landt O, Schmit CA. LightCycler technology for the quantitation of bcr/abl fusion transcripts. Cancer Res. 1999;59:317–74.

    Google Scholar 

  24. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M. A role of the afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology. 2002;123:1120–8.

    Article  CAS  PubMed  Google Scholar 

  25. Zhang JV, Ren P-G, Avsian-Kretchmer O, Luo C-W, Rauch R, Klein C, et al. Obestatin, peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food Intake. Science. 2005;310:996–9.

    Article  CAS  PubMed  Google Scholar 

  26. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes. 2001;50:1714–9.

    Article  CAS  PubMed  Google Scholar 

  27. Richardson CT, Walsh JH, Hicks MI, Fordtran JS. Studies on the mechanisms of food-stimulated acid secretion in normal human subjects. J Clin Invest. 1976;58:623–31.

    Article  CAS  PubMed  Google Scholar 

  28. Levi S, Beardshall K, Swift I, Foulkes W, Playford R, Ghosh P, et al. Antral Helicobacter pylori, hypergastrinaemia and duodenal ulcer: effect of eradicating the organism. BMJ. 1989;299:1904–5.

    Google Scholar 

Download references

Acknowledgments

We are very grateful to Mrs Mitsuko Kudo for her assistance in preparing this manuscript and for her assistance in the animal experiments.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tomoya Sakurada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakurada, T., Ro, S., Onouchi, T. et al. Comparison of the actions of acylated and desacylated ghrelin on acid secretion in the rat stomach. J Gastroenterol 45, 1111–1120 (2010). https://doi.org/10.1007/s00535-010-0269-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-010-0269-6

Keywords

Navigation