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. 1997 Aug 15;503(Pt 1):169–175. doi: 10.1111/j.1469-7793.1997.169bi.x

Increased sensitivity of gastrin cells to gastric distension following antral denervation in the rat.

A Higham 1, P Noble 1, D G Thompson 1, G J Dockray 1
PMCID: PMC1159896  PMID: 9288684

Abstract

1. Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relative importance of luminal and neuronal mechanisms, by lesioning the antral innervation using benzalkonium chloride. 2. Benzalkonium chloride was applied to the serosa of the antrum in anaesthetized rats. In some animals, a stainless-steel cannula was also implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and histidine decarboxylase were measured by Northern blot. 3. Antral denervation was associated with gastric retention after fasting, and elevated plasma gastrin (28.4 +/- 7 pM compared with 7.6 +/- 1.0 pM in controls). When fasted control or denervated rats were refed, plasma gastrin increased 3-fold in both cases. A gastrin-releasing peptide antagonist inhibited the post-prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats. 4. In fasted, antrally denervated rats with a gastric fistula, basal gastric acid secretion was depressed 3-fold, and plasma gastrin concentrations were similar to controls. 5. Distension of the stomach with peptone via a barostat attached to the gastric cannula (5 cm H2O, 30 min), produced 3-fold increases in plasma gastrin in both control and denervated rats. However, distension with a non-nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a similar extent to peptone in denervated rats; distension with 50 mM HCl had no effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA abundances in the antrum were depressed by about 35% by antral denervation, but somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffected by antral denervation. 7. The data suggest that luminal nutrient releases gastrin in the rat, in vivo, via activation of antral neurons secreting gastrin-releasing peptide, and that the antral innervation normally inhibits G-cell responses to non-nutrient distension of the stomach. After antral denervation, gastric distension with a non-nutrient solution is an adequate stimulus for gastrin release.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BULBRING E., LIN R. C. The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis; the local production of 5-HT and its release in relation to intraluminal pressure and propulsive activity. J Physiol. 1958 Mar 11;140(3):381–407. [PMC free article] [PubMed] [Google Scholar]
  2. Bate G. W., Varro A., Dimaline R., Dockray G. J. Control of preprogastrin messenger RNA translation by gastric acid in the rat. Gastroenterology. 1996 Nov;111(5):1224–1229. doi: 10.1053/gast.1996.v111.pm8898636. [DOI] [PubMed] [Google Scholar]
  3. Brand S. J., Stone D. Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria. J Clin Invest. 1988 Sep;82(3):1059–1066. doi: 10.1172/JCI113662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brodie D. A., Knapp P. G. The mechanism of the inhibition of gastric secretion produced by esophageal ligation in the pylorus-ligated rat. Gastroenterology. 1966 Jun;50(6):787–795. [PubMed] [Google Scholar]
  5. Chiba T., Taminato T., Kadowaki S., Abe H., Chihara K., Seino Y., Matsukura S., Fujita T. Effects of glucagon, secretin, and vasoactive intestinal polypeptide on gastric somatostatin and gastrin release from isolated perfused rat stomach. Gastroenterology. 1980 Jul;79(1):67–71. [PubMed] [Google Scholar]
  6. Debas H. T., Walsh J. H., Grossman M. I. Evidence for oxyntopyloric reflex for release of antral gastrin. Gastroenterology. 1975 Apr;68(4 Pt 1):687–690. [PubMed] [Google Scholar]
  7. DelValle J., Yamada T. Amino acids and amines stimulate gastrin release from canine antral G-cells via different pathways. J Clin Invest. 1990 Jan;85(1):139–143. doi: 10.1172/JCI114404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dimaline R., Carter N., Barnes S. Evidence for reflex adrenergic inhibition of acid secretion in the conscious rat. Am J Physiol. 1986 Nov;251(5 Pt 1):G615–G618. doi: 10.1152/ajpgi.1986.251.5.G615. [DOI] [PubMed] [Google Scholar]
  9. Dimaline R., Evans D., Forster E., Dockray G. J. Stimulation of gastric somatostatin mRNA abundance by substance P in capsaicin-treated rats. Neurosci Lett. 1994 May 19;172(1-2):39–41. doi: 10.1016/0304-3940(94)90657-2. [DOI] [PubMed] [Google Scholar]
  10. Dimaline R., Evans D., Varro A., Dockray G. J. Reversal by omeprazole of the depression of gastrin cell function by fasting in the rat. J Physiol. 1991 Feb;433:483–493. doi: 10.1113/jphysiol.1991.sp018439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dimaline R., Sandvik A. K., Evans D., Forster E. R., Dockray G. J. Food stimulation of histidine decarboxylase messenger RNA abundance in rat gastric fundus. J Physiol. 1993 Jun;465:449–458. doi: 10.1113/jphysiol.1993.sp019686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dockray G. J., Hamer C., Evans D., Varro A., Dimaline R. The secretory kinetics of the G cell in omeprazole-treated rats. Gastroenterology. 1991 May;100(5 Pt 1):1187–1194. [PubMed] [Google Scholar]
  13. Dockray G. J., Tracy H. J. Atropine does not abolish cephalic vagal stimulation of gastrin release in dogs. J Physiol. 1980 Sep;306:473–480. doi: 10.1113/jphysiol.1980.sp013408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dockray G. J., Vaillant C., Walsh J. H. The neuronal origin of bombesin-like immunoreactivity in the rat gastrointestinal tract. Neuroscience. 1979;4(11):1561–1568. doi: 10.1016/0306-4522(79)90019-8. [DOI] [PubMed] [Google Scholar]
  15. Dockray G. J., Varro A., Dimaline R. Gastric endocrine cells: gene expression, processing, and targeting of active products. Physiol Rev. 1996 Jul;76(3):767–798. doi: 10.1152/physrev.1996.76.3.767. [DOI] [PubMed] [Google Scholar]
  16. Farooq O., Walsh J. H. Atropine enhances serum gastrin response to insulin in man. Gastroenterology. 1975 Apr;68(4 Pt 1):662–666. [PubMed] [Google Scholar]
  17. Feldman M., Richardson C. T., Taylor I. L., Walsh J. H. Effect of atropine on vagal release of gastrin and pancreatic polypeptide. J Clin Invest. 1979 Feb;63(2):294–298. doi: 10.1172/JCI109302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Feurle G. E., Tischbirek K., Baća I. G-cell hyperplasia in rats with pyloric stenosis. Dig Dis Sci. 1988 Jul;33(7):795–800. doi: 10.1007/BF01550965. [DOI] [PubMed] [Google Scholar]
  19. Higham A., Vaillant C., Yegen B., Thompson D. G., Dockray G. J. Relation between cholecystokinin and antral innervation in the control of gastric emptying in the rat. Gut. 1997 Jul;41(1):24–32. doi: 10.1136/gut.41.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Holst J. J., Harling H., Messell T., Coy D. H. Identification of the neurotransmitter/neuromodulator functions of the neuropeptide gastrin-releasing peptide in the porcine antrum, using the antagonist (Leu13-psi-CH2 NH-Leu14)-bombesin. Scand J Gastroenterol. 1990 Jan;25(1):89–96. doi: 10.3109/00365529008999214. [DOI] [PubMed] [Google Scholar]
  21. Kirchgessner A. L., Tamir H., Gershon M. D. Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity. J Neurosci. 1992 Jan;12(1):235–248. doi: 10.1523/JNEUROSCI.12-01-00235.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lichtenberger L. M., Delansorne R., Graziani L. A. Importance of amino acid uptake and decarboxylation in gastrin release from isolated G cells. Nature. 1982 Feb 25;295(5851):698–700. doi: 10.1038/295698a0. [DOI] [PubMed] [Google Scholar]
  23. Lichtenberger L. M. Importance of food in the regulation of gastrin release and formation. Am J Physiol. 1982 Dec;243(6):G429–G441. doi: 10.1152/ajpgi.1982.243.6.G429. [DOI] [PubMed] [Google Scholar]
  24. Moody T. W., Venugopal R., Zia F., Patierno S., Leban J. J., McDermed J. BW2258U89: a GRP receptor antagonist which inhibits small cell lung cancer growth. Life Sci. 1995;56(7):521–529. doi: 10.1016/0024-3205(94)00481-7. [DOI] [PubMed] [Google Scholar]
  25. Saffouri B., DuVal J. W., Makhlouf G. M. Stimulation of gastrin secretion in vitro by intraluminal chemicals: regulation by intramural cholinergic and noncholinergic neurons. Gastroenterology. 1984 Sep;87(3):557–561. [PubMed] [Google Scholar]
  26. Saffouri B., Weir G. C., Bitar K. N., Makhlouf G. M. Gastrin and somatostatin secretion by perfused rat stomach: functional linkage of antral peptides. Am J Physiol. 1980 Jun;238(6):G495–G501. doi: 10.1152/ajpgi.1980.238.6.G495. [DOI] [PubMed] [Google Scholar]
  27. Sandvik A. K., Dimaline R., Forster E. R., Evans D., Dockray G. J. Differential control of somatostatin messenger RNA in rat gastric corpus and antrum. Role of acid, food, and capsaicin-sensitive afferent neurons. J Clin Invest. 1993 Jan;91(1):244–250. doi: 10.1172/JCI116177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schiller L. R., Walsh J. H., Feldman M. Distention-induced gastrin release: effects of luminal acidification and intravenous atropine. Gastroenterology. 1980 May;78(5 Pt 1):912–917. [PubMed] [Google Scholar]
  29. Schubert M. L., Coy D. H., Makhlouf G. M. Peptone stimulates gastrin secretion from the stomach by activating bombesin/GRP and cholinergic neurons. Am J Physiol. 1992 Apr;262(4 Pt 1):G685–G689. doi: 10.1152/ajpgi.1992.262.4.G685. [DOI] [PubMed] [Google Scholar]
  30. Schubert M. L., Jong M. J., Makhlouf G. M. Bombesin/GRP-stimulated somatostatin secretion is mediated by gastrin in the antrum and intrinsic neurons in the fundus. Am J Physiol. 1991 Nov;261(5 Pt 1):G885–G889. doi: 10.1152/ajpgi.1991.261.5.G885. [DOI] [PubMed] [Google Scholar]
  31. Schubert M. L., Makhlouf G. M. Gastrin secretion induced by distention is mediated by gastric cholinergic and vasoactive intestinal peptide neurons in rats. Gastroenterology. 1993 Mar;104(3):834–839. doi: 10.1016/0016-5085(93)91020-i. [DOI] [PubMed] [Google Scholar]
  32. Wade P. R., Chen J., Jaffe B., Kassem I. S., Blakely R. D., Gershon M. D. Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci. 1996 Apr 1;16(7):2352–2364. doi: 10.1523/JNEUROSCI.16-07-02352.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wu S. V., Giraud A., Mogard M., Sumii K., Walsh J. H. Effects of inhibition of gastric secretion on antral gastrin and somatostatin gene expression in rats. Am J Physiol. 1990 May;258(5 Pt 1):G788–G793. doi: 10.1152/ajpgi.1990.258.5.G788. [DOI] [PubMed] [Google Scholar]
  34. Zhao C. M., Chen D., Monstein H. J., Ding X. Q., Sundler F., Håkanson R. Rat stomach enterochromaffin-like cells are not stimulated by pylorus ligation. A biochemical and ultrastructural study. Scand J Gastroenterol. 1996 Jan;31(1):31–37. doi: 10.3109/00365529609031623. [DOI] [PubMed] [Google Scholar]

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