Skip to main content
SpringerLink
Log in

The Effect of Resiniferatoxin on Experimental Gastric Ulcer in Rats

  • Chapter
Biochemical Pharmacology as an Approach to Gastrointestinal Disorders

Abstract

Capsaicin-sensitive sensory nerves are involved in modulation of gastric mucosal integrity. The present study aimed to evaluate the effect of the capsaicin analogue, resiniferatoxin (RTX), on gastric mucosal damage produced by different ulcerogenic agents in the rat. Gastric mucosal damage was evoked in pylorus-ligated rats by the administration of intragastric (ig) HC1 (2 ml of 0.6 N), ig ethanol (2 ml of 96% or 50% v/v), ig acidified aspirin (200 mg/kg dissolved in 2 ml of 0.15 HCl), subcutaneous (sc) aspirin (200 mg/kg plus ig 2 ml of 0.15 N HС1) and sc indomethacin (20 mg/kg). Animals were sacrificed at different time intervals after administration of the above ulcerogens, when gastric secretory responses, and the number and severity of mucosal lesions were noted. Intragastric RTX (0.6–2 µg/kg) protected against mucosal injury by 0.6 N HС1 in a dose-dependent manner. Resiniferatoxin at 0.4 µg/ kg prevented mucosal injury by sc indomethacin or sc aspirin in the 4-h pylorus-ligated rat. Resiniferatoxin (0.6 and 1 µg/kg) co-administered with ethanol reduced mucosal injury caused by 50% ethanol. The protective effect of RTX was more marked if the drug was given 15 min prior to ethanol. Resiniferatoxin protected against damage by 96% ethanol if given 15 min prior to challenge, but, when co-administered with 96% ethanol, RTX aggravated the ethanol-induced mucosal damage. Resiniferatoxin by itself did not produce visible gastric mucosal damage in the saline-treated controls. Data indicated that the capsaicin analogue, resiniferatoxin, exerts potent gastroprotective effects in various experimental ulcer models in the rat.

Correspondence

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Szolcśanyi J. Capsaicin, irritation, and desensitization: Neurophysiological basis and future perspectives. In: Green BG, Mason JR, Kare MR, eds. Chemical Senses. Irritation. Vol. 2. New York: Marcel Dekker; 1989: 141–69.

    Google Scholar 

  2. Szolcśanyi J. Actions of capsaicin on sensory receptors. In: Wood JN, ed. Capsaicin in the Study of Pain. Neuroscience Perspectives. London: Academic Press; 1993: 1–23.

    Google Scholar 

  3. Holzer P. Capsaicin, cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev. 1991; 43: 143–201.

    PubMed  CAS  Google Scholar 

  4. Szolcśanyi J, Barthó L. Impaired defense mechanism to peptic ulcer in the capsaicin-desensitized rat. In: Mózsik Gy, Hänninen O, Jávor T, eds. Gastrointestinal Defense Mechanisms. Oxford and Budapest: Pergamon Press and Akademiai Kiadó; 1980: 39–51.

    Google Scholar 

  5. Holzer P, Lippe IT. Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa. Neuroscience. 1988; 27: 981–7.

    Article  PubMed  CAS  Google Scholar 

  6. Holzer P, Sametz W. Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive neurons. Gastroenterology. 1986; 91: 975–81.

    PubMed  CAS  Google Scholar 

  7. Gray JL, Bunnett NW, Orloff SL, Mulvihill SJ, Debas HT. Role of calcitonin gene-related peptide in protection against gastric ulceration. Ann Surg. 1994; 219: 58–64.

    Article  PubMed  CAS  Google Scholar 

  8. Holzer P, Pabst MA, Lippe IT. Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa. Gastroenterology. 1989; 96: 1425–33.

    PubMed  CAS  Google Scholar 

  9. Szolcśanyi J. Effect of capsaicin, resiniferatoxin and piperine on ethanol-induced gastric ulcer of the rat. Acta Physiol Hung. 1990; 75 (Suppl): 267–8.

    PubMed  Google Scholar 

  10. Sternini C, Reeve JR, Brecha N. Distribution and characterization of calcitonin gene-related peptide immunoreactivity in the digestive system of normal and capsaicin-treated rats. Gastroenterology. 1987; 93: 852–862.

    PubMed  CAS  Google Scholar 

  11. Green T, Dockray GJ. Characterization of the peptidergic afferent innervation of the stomach in the rat, mouse and guinea pig. Neuroscience. 1988; 25: 181–93.

    Article  PubMed  CAS  Google Scholar 

  12. Holzer P, Peskar BM, Peskar BA, Amann R. Release of calcitonin gene-related peptide induced by capsaicin in the vascularly perfused rat stomach. Neurosci Lett. 1990; 108: 195–200.

    Article  PubMed  CAS  Google Scholar 

  13. Renzi D, Santicioli P, Maggi CA, Surrenti C, Pradelles P, Meli A. Capsaicin-induced release of substance P-like immunoreactivity from guinea pig stomach in vitro and in vivo. Neurosci Lett. 1988; 92: 254–8.

    Article  PubMed  CAS  Google Scholar 

  14. Lippe IT, Pabst MA, Holzer P. Intragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation. Br J Pharmacol. 1989; 96: 91–100.

    Article  PubMed  CAS  Google Scholar 

  15. Holzer P, Livingstone EH, Saria A, Guth PH. Sensory neurons mediate protective vasodilatation in rat gastric mucosa. Am J Physiol. 1991; 260: G363–70.

    PubMed  CAS  Google Scholar 

  16. Li DS, Raybould HE, Quintero E, Guth PH. Role of calcitonin gene-related peptide in the gastric hyperemic response to intragastric capsaicin. Am J Physiol. 1991; 261: G657–61.

    PubMed  CAS  Google Scholar 

  17. Chen RYZ, Li DS, Guth PH. Role of calcitonin gene-related peptide in capsaicin-induced gastric submucosal arteriolar dilatation. Am J Physiol. 1992;262LH1350–5.

    Google Scholar 

  18. Schmidt RJ, Evans FJ. A new aromatic ester diterpene from Eurphorbia poisonii. Phytochemistry. 1976; 15: 1778–9.

    Article  CAS  Google Scholar 

  19. Szallasi A, Blumberg PM. Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes. Brain Res. 1990; 524: 109–11.

    Article  Google Scholar 

  20. Szolcśanyi J, Szallasi A, Szallasi Z, Joo F, Blumberg PM. Resiniferatoxin: an ultrapotent selective modulator of capsaicin-sensitive primary afferent neurons. J Pharmacol Exp Ther. 1990; 255: 923–8.

    PubMed  Google Scholar 

  21. Szallasi A, Blumberg PM. Mechanisms and therapeutic potential of vanilloids (capsaicin-like molecules). Adv Pharmacol. 1992; 24: 123–55.

    Article  Google Scholar 

  22. Mózsik Gy, Móron F, Jávor T. Cellular mechanisms of the development of gastric mucosal damage and of gastric cytoprotection induced by prostacyclin in rats. A pharmacological study. Prostagl Leukotrienes Med. 1982; 9: 71–84.

    Article  Google Scholar 

  23. Davenport HW Ethanol damage to canine oxyntic glandular mucosa. Proc Soc Exp Biol Med. 1967; 126: 657–62.

    CAS  Google Scholar 

  24. Abdel-Salam OME, Bódis B, Karádi O, Nagy L, Szolcśanyi J, Mózsik Gy. Stimulation of capsaicinsensitive sensory peripheral nerves with topically applied resiniferatoxin decreases salicylate-induced gastric H+ back-diffusion in the rat. Inflammopharmacology. 1995; 3: 121–33.

    Article  CAS  Google Scholar 

  25. Abdel-Salam OME, Bódis B, Karádi O, Szolcsányi J, Mózsik Gy. Modification of aspirin and ethanol-induced mucosal damage in rats by intragastric application of resiniferatoxin. Inflammopharmacology. 1995; 3: 135–47.

    Article  CAS  Google Scholar 

  26. Ritchie WP Jr. Acute gastric mucosal damage induced by bile salts, acid and ischaemia. Gastroenterology. 1975; 68: 699–707.

    PubMed  Google Scholar 

  27. Leung FW, Itoh M, Hirabayashi K, Guth PH. Role of blood flow in gastric and duodenal injury in the rat. Gastroenterology. 1985; 88: 281–9.

    PubMed  CAS  Google Scholar 

  28. Guth PH, Paulsen G, Nagata H. Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: effect of prostaglandin cytoprotection. Gastroenterology. 1984; 87: 1083–90.

    PubMed  CAS  Google Scholar 

  29. Ohya Y, Guth PH. Ethanol-induced gastric mucosal blood flow and vascular permeability changes in the rat. Dig Dis Sci. 1988; 33: 883–8.

    Article  PubMed  CAS  Google Scholar 

  30. Trier JS, Szabó S, Allan CH. Ethanol-induced damage to mucosal capillaries of rat stomach. Ultrastructural features and effect of prostaglandin F2β and cysteamine. Gastroenterology. 1987; 92: 13–22.

    PubMed  CAS  Google Scholar 

  31. Oates P3, Hakkinen JP. Studies on the mechanism of ethanol-induced gastric damage in rats. Gastroenterology. 1988; 94: 10–21.

    PubMed  CAS  Google Scholar 

  32. Bou-Abboud CF, Wayland H, Paulsen G, Guth PH. Microcirculatory stasis precedes tissue necrosis in ethanol-induced gastric mucosal injury in the rat. Dig Dis Sci. 1988; 33: 872–7.

    Article  PubMed  CAS  Google Scholar 

  33. Kauffman GL, Aures Jr D, Grossman MI. Intravenous indomethacin and aspirin reduce basal gastric mucosal blood flow in dogs. Am J Physiol. 1980; 238: G131–4.

    PubMed  CAS  Google Scholar 

  34. Ashley SW, Sonnenschein LA, Leung LY. Focal gastric mucosal blood flow at the site of aspirin-induced ulceration. Am J Sig. 1985; 149: 53–9.

    CAS  Google Scholar 

  35. Kitahora T, Guth PH. Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation. Gastroenterology. 1987; 93: 810–17.

    PubMed  CAS  Google Scholar 

  36. Whittle BJR. Mechanisms underlying gastric mucosal damage induced by indomethacin and bile salts, and the actions of prostaglandins. Br J Pharmacol. 1977; 60: 455–60.

    Article  PubMed  CAS  Google Scholar 

  37. Hirose H, Takeuchi K, Okabe S. Effect of indomethacin on gastric mucosal blood flow around acetic acid-induced gastric ulcers in rats. Gastroenterology. 1991; 100: 1259–65.

    PubMed  CAS  Google Scholar 

  38. Shorrock CJ, Rees WSW. Mucosal adaptation to indomethacin induced gastric damage in man-studies on morphology, blood flow, and prostaglandin metabolism. Gut. 1992; 33: 164–9.

    Article  PubMed  CAS  Google Scholar 

  39. Tarnawski A, Stachura J, Gergely H, Hollander D. Gastric mucosal epithelium: a major target for aspirin-induced injury and arachidonic acid protection, and ultrastructural analysis in the rat. Eur J Chem Invest. 1990; 20: 432–40.

    Article  CAS  Google Scholar 

  40. Wallace IL, Keenan CM, Granger DN. Gastric ulceration induced by nonsteroid anti-inflammatory drugs is a neutrophil dependent mechanism. Am J Physiol. 1990; 259: G462–7.

    PubMed  CAS  Google Scholar 

  41. Whittle BJR, Higgs GA, Eakins KE, Moncada S, Vane JR. Selective inhibition of prostaglandin production in inflammatory exudates and gastric mucosa. Nature. 1980; 284: 271–3.

    Article  PubMed  CAS  Google Scholar 

  42. Main IHM, Whittle BJR. Investigation of the vasodilator and antisecretory role of prostaglandins in the rat gastric mucosa by use of non-steroidal anti-inflammatory drugs. Br J Pharmacol. 1977; 60: 45560.

    Google Scholar 

  43. Abdel-Salam OME, Szolcśanyi J, Mózsik Gy. Effect of resiniferatoxin on stimulated gastric acid secretory responses in the rat. J Physiology (Paris). 1995; 88: 353–8.

    Article  Google Scholar 

  44. Guth PH, Aures D, Paulsen G. Topical aspirin plus HC1 gastric lesions in the rat. Gastroenterology. 1977; 76: 88–93.

    Google Scholar 

  45. Szabó S, Goldberg I. Experimental pathogenesis: drugs and chemical lesions in the gastric mucosa. Scand J Gastroenterol. 1990; 25 (Suppl 174): 1–8.

    Article  Google Scholar 

  46. Brain SD, Williams TJ. Inflammatory oedema induced by synergism between calcitonin gene-related peptide (CGRP) and mediators of increased microvascular permeability. Br J Pharmacol. 1985; 86: 855–900.

    Article  PubMed  CAS  Google Scholar 

  47. Buckley TL, Brain SD, Rampart M, Williams TJ. Time-dependent synergistic interactions between the vasodilator neuropeptide, calcitonin gene-related peptide (CGRP) and mediators of inflammation Br J Pharmacol. 1991; 103: 1515–19.

    Article  PubMed  CAS  Google Scholar 

  48. Newbold P, Brain SD. The modulation of inflammatory oedema by calcitonin gene-related peptide. Br J Pharmacol. 1993; 108: 705–10.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Medicine, Medical University of Pécs, Ifjúság út, H-7643, Pécs, Hungary

    O. M. E. Abdel-Salam & Gy. Mózsik

  2. Department of Pharmacology, Medical University of Pécs, Ifjúság út, H-7643, Pécs, Hungary

    J. Szolcsányi

Authors
  1. O. M. E. Abdel-Salam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Szolcsányi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gy. Mózsik
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Pharmacy, University of Wisconsin, Madison, WI, USA

    Timothy S. Gaginella

  2. First Department of Medicine, University Medical School of Pécs, Pécs, Hungary

    Gyula Mózsik

  3. Department of Biomedical Sciences, Sheffield Hallam University, Sheffield, UK

    K. D. Rainsford

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Abdel-Salam, O.M.E., Szolcsányi, J., Mózsik, G. (1997). The Effect of Resiniferatoxin on Experimental Gastric Ulcer in Rats. In: Gaginella, T.S., Mózsik, G., Rainsford, K.D. (eds) Biochemical Pharmacology as an Approach to Gastrointestinal Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5390-4_22

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-5390-4_22

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6267-1

  • Online ISBN: 978-94-011-5390-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation