Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Feb;77(2):436–440. doi: 10.1172/JCI112322

Interactions of bombesin and substance P at the feline lower esophageal sphincter.

J C Reynolds, M R Dukehart, A Ouyang, S Cohen
PMCID: PMC423364  PMID: 2418063

Abstract

The purpose of this study was to determine the interactions between bombesin and substance P at the feline lower esophageal sphincter (LES). Intraluminal pressures were recorded using a fixed, perfused catheter assembly. Myoelectrical activity was recorded using bipolar Ag-AgCl serosal electrodes. Bombesin, i.v., gave a dose-dependent increase in LES pressure and electronically counted spike activity. The threshold dose was 10(-7) g/kg, while the maximal dose, 10(-5) g/kg, increased LES pressure by 65.5 +/- 14.8 mmHg. The neuroantagonist, tetrodotoxin, decreased the LES response to bombesin by 74.1% +/- 7.9% (P less than 0.05), but had no significant effect on the LES response to substance P. The sphincteric response to bombesin was not inhibited by bilateral cervical vagotomy, atropine, propranolol, or phentolamine (P less than 0.10). Bombesin tachyphylaxis abolished the LES response to bombesin but had no effect on the response to substance P. Conversely, substance P tachyphylaxis completely abolished the LES response to bombesin (P less than 0.001). The substance P antagonist [D-Pro2, D-Trp7,9]substance P also significantly inhibited the LES response to bombesin (P less than 0.05). Acidification of the distal esophagus with 2.0 ml of 0.1 N HCl increased LES pressure by 32.5 +/- 5.2 mmHg (P less than 0.02). The LES response to acid was inhibited by bombesin tachyphylaxis (maximal pressure response, 4.7 +/- 2.1 mmHg, P less than 0.01 compared with control acid response). The tachyphylaxis techniques were specific for the peptides giving no effect on the LES responses to phenylephrine, bethanechol, or pentagastrin. We drew the following conclusions: (a) bombesin increased feline LES pressure via nonvagal neural pathways that were insensitive to adrenergic or cholinergic antagonists; (b) bombesin may be involved in the enteric pathways that mediate the feline LES response to distal esophageal acidification; and (c) substance P mediates the effect of bombesin at the LES and is a neurotransmitter in the LES response to acidification.

Full text

PDF
437

Selected References

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

  1. Ahtaridis G., Snape W. J., Jr, Cohen S. Lower esophageal sphincter pressure as an index of gastroesophageal acid reflux. Dig Dis Sci. 1981 Nov;26(11):993–998. doi: 10.1007/BF01314761. [DOI] [PubMed] [Google Scholar]
  2. Angel F., Go V. L., Szurszewski J. H. Innervation of the muscularis mucosae of canine proximal colon. J Physiol. 1984 Dec;357:93–108. doi: 10.1113/jphysiol.1984.sp015491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buffa R., Solovieva I., Fiocca R., Giorgino S., Rindi G., Solcia E., Mochizuchi T., Yanaihara C., Yanaihara N. Localization of bombesin and GRP (gastrin releasing peptide) sequences in gut nerves or endocrine cells. Histochemistry. 1982;76(4):457–467. doi: 10.1007/BF00489901. [DOI] [PubMed] [Google Scholar]
  4. Corazziari E., Delle Fave G., Pozzessere C., Kohn A., de Magistris L., Anzini F., Torsoli A. Effect of bombesin on lower esophageal sphincter pressure in humans. Gastroenterology. 1982 Jul;83(1 Pt 1):10–14. [PubMed] [Google Scholar]
  5. Costa M., Furness J. B., Llewellyn-Smith I. J., Cuello A. C. Projections of substance P-containing neurons within the guinea-pig small intestine. Neuroscience. 1981;6(3):411–424. doi: 10.1016/0306-4522(81)90134-2. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Leander S., Håkanson R., Rosell S., Folkers K., Sundler F., Tornqvist K. A specific substance P antagonist blocks smooth muscle contractions induced by non-cholinergic, non-adrenergic nerve stimulation. Nature. 1981 Dec 3;294(5840):467–469. doi: 10.1038/294467a0. [DOI] [PubMed] [Google Scholar]
  8. Lee P. C., Jensen R. T., Gardner J. D. Bombesin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas. Am J Physiol. 1980 Mar;238(3):G213–G218. doi: 10.1152/ajpgi.1980.238.3.G213. [DOI] [PubMed] [Google Scholar]
  9. Lundberg J. M., Martling C. R., Saria A. Substance P and capsaicin-induced contraction of human bronchi. Acta Physiol Scand. 1983 Sep;119(1):49–53. doi: 10.1111/j.1748-1716.1983.tb07304.x. [DOI] [PubMed] [Google Scholar]
  10. Mayer E. A., Elashoff J., Walsh J. H. Characterization of bombesin effects on canine gastric muscle. Am J Physiol. 1982 Aug;243(2):G141–G147. doi: 10.1152/ajpgi.1982.243.2.G141. [DOI] [PubMed] [Google Scholar]
  11. Moghimzadeh E., Ekman R., Håkanson R., Yanaihara N., Sundler F. Neuronal gastrin-releasing peptide in the mammalian gut and pancreas. Neuroscience. 1983 Oct;10(2):553–563. doi: 10.1016/0306-4522(83)90152-5. [DOI] [PubMed] [Google Scholar]
  12. Mukhopadhyay A. K., Kunnemann M. Mechanism of lower esophageal sphincter stimulation by bombesin in the opossum. Gastroenterology. 1979 Jun;76(6):1409–1414. [PubMed] [Google Scholar]
  13. Panula P., Hadjiconstantinou M., Yang H. Y., Costa E. Immunohistochemical localization of bombesin/gastrin-releasing peptide and substance P in primary sensory neurons. J Neurosci. 1983 Oct;3(10):2021–2029. doi: 10.1523/JNEUROSCI.03-10-02021.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Poitras P., Tassé D., Laprise P. Stimulation of motilin release by bombesin in dogs. Am J Physiol. 1983 Aug;245(2):G249–G256. doi: 10.1152/ajpgi.1983.245.2.G249. [DOI] [PubMed] [Google Scholar]
  15. Porreca F., Burks T. F. Centrally administered bombesin affects gastric emptying and small and large bowel transit in the rat. Gastroenterology. 1983 Aug;85(2):313–317. [PubMed] [Google Scholar]
  16. Reeve J. R., Jr, Walsh J. H., Chew P., Clark B., Hawke D., Shively J. E. Amino acid sequences of three bombesin-like peptides from canine intestine extracts. J Biol Chem. 1983 May 10;258(9):5582–5588. [PubMed] [Google Scholar]
  17. Reynolds J. C., Ouyang A., Cohen S. A lower esophageal sphincter reflex involving substance P. Am J Physiol. 1984 Apr;246(4 Pt 1):G346–G354. doi: 10.1152/ajpgi.1984.246.4.G346. [DOI] [PubMed] [Google Scholar]
  18. Wood S. M., Jung R. T., Webster J. D., Ghatei M. A., Adrian T. E., Yanaihara N., Yanaihara C., Bloom S. R. The effect of the mammalian neuropeptide, gastrin-releasing peptide (GRP), on gastrointestinal and pancreatic hormone secretion in man. Clin Sci (Lond) 1983 Oct;65(4):365–371. doi: 10.1042/cs0650365. [DOI] [PubMed] [Google Scholar]
  19. Zappia L., Molina E., Sianesi M., Bertaccini G. Effects of natural analogues of substance P on the motility of human gastrointestinal tract in vitro. J Pharm Pharmacol. 1978 Sep;30(9):593–594. doi: 10.1111/j.2042-7158.1978.tb13335.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES