Skip to main content
SpringerLink
Log in

Mechanisms of Transforming Growth Factor-α (TGF-α) Induced Gastroprotection Against Ethanol in the Rat: Roles of Sensory Neurons, Sensory Neuropeptides, and Prostaglandins

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The mechanisms by which transforming growth factor-α (TGF-α) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFα gastroprotection against ethanol. Fasted rats received TGF-α (50 μg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-α-mediated gastroprotection. TGF-α significantly diminished ethanol-induced gastric lesion area to 5.7 ± 0.8 mm2 vs 4l.1 ± 5.2 mm2 (P < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-α protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-α gastroprotection. In conclusion, TGF-α-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Karnes WE Jr: Epidermal growth factor and transforming growth factorα. In Gut Peptides: Biochemistry and Physiology. JH Walsh, GI Dockray (eds). New York, Raven Press, 1994, pp. 553-586

    Google Scholar 

  2. Beauchamp RD, Bernard JA, McCutchen CM, Cherner JA, Coffey RJ: Localization of TGFα and its receptor in gastric mucosal cells: implication for a regulatory role in acid secretion and mucosal renewal. J Clin Invest 84:1017-1023, 1990

    Google Scholar 

  3. Polk WH, Saroka CJ, Goldenring J: Immunolocalization of transforming growth factor alpha (TGF-alpha) and its receptor to the parietal in normal gastric mucosa. Gastroenterology 100:A660(abstract), 1991

    Google Scholar 

  4. Romano M, Polk WH, Awad JA, Arteaga CL, Nanney LB, Wargovich MJ, Kraus ER, Boland CR, Coffey RJ: Transforming growth factor-α protection against drug-induced injury to rat gastric mucosa in vivo. J Clin Invest 90:2409-2421, 1992

    Google Scholar 

  5. Polk WH, Dempsey PJ, Russell WE, Brown PI, Beauchamp D, Bernard JA, Coffey RJ: Increase production of transforming growth factor alpha following acute gastric injury. Gastroenterology 102:1467-1474, 1992

    Google Scholar 

  6. Konturek PC, Ernst H, Brzozowski T, Ihlm A, Hahn EG, Konturek SJ: Expression of epidermal growth factor and transforming growth factor alpha after exposure of rat gastric mucosa to stress. Scand J Gastroenterol 31:209-216, 1996

    Google Scholar 

  7. Konturek SJ, Brzozowski T, Majka J, Dembinski A, Slomiany A, Slonciany BL: Transforming growth factor alpha and epidermal growth factor in protection and healing of gastric mucosal injury. Scand J Gastroenterol 27:649-655, 1992

    Google Scholar 

  8. Tepperman BL, Soper BD: Effect of epidermal growth factor, transforming growth factor α and nerve growth factor on gastric mucosal integrity and microcirculation in the rat. Regul Pep 50:13-21, 1994

    Google Scholar 

  9. Kang JY, Teng CH, Chen FC, Wee A: Role of capsaicin-sensitive nerve in epidermal growth factor effects on gastric mucosal injury and blood flow. Gut 42:344-350, 1998

    Google Scholar 

  10. Matsumoto Y, Kanamoto K, Kawakubo K, Aomi H, Matsumoto T, Iboyoshi S, Fujishima M: Gastroprotective and vasodilatory effects of epidermal growth factor: the role of sensory afferent neurons. Am J Physiol 280:G897-G903, 2001

    Google Scholar 

  11. Ren J, Gao J, Ojeas H, Lightfoot SA, Kida M, Brewer K, Harty RF: Involvement of capsaicin-sensitive neurons in stress-induced gastroduodenal mucosal injury in rats. Dig Dis Sci 45:830-836, 2000

    Google Scholar 

  12. Martinez-Cuesta MA, Barrachina MD, Beltran B, Calatayud S, Espluges J: Nitric oxide modulates the acute increase of gastrointestinal transit induced by endotoxin in rats: a possible role for tachykinins. J Pharm Pharmacol 49:988-990, 1997

    Google Scholar 

  13. Playford RJ, Hanby AM, Gschmeissner S, Peiffer LP, Wright NA, McGarrity T: The epidermal growth factor (EGF-R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract. Gut 39:262-266, 1996

    Google Scholar 

  14. Ren J, Xia Y, Mesiya S, Dunn T, Harty RF: Functional interactions between transforming growth factor-α and gastric sensory neurons. Gastroenterology 116:G2662(abstract), 1999.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of Oklahoma Health Sciences Center, USA

    Verapan Vongthavaravat, Sikandar Mesiya, Layth Saymeh & Yang Xia

  2. Oklahoma City Department of Veterans Affairs, Medical Center, Oklahoma City, Oklahoma, USA

    Verapan Vongthavaravat, Sikandar Mesiya, Layth Saymeh, Yang Xia & Richard F. Harty

Authors
  1. Verapan Vongthavaravat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sikandar Mesiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Layth Saymeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard F. Harty
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vongthavaravat, V., Mesiya, S., Saymeh, L. et al. Mechanisms of Transforming Growth Factor-α (TGF-α) Induced Gastroprotection Against Ethanol in the Rat: Roles of Sensory Neurons, Sensory Neuropeptides, and Prostaglandins. Dig Dis Sci 48, 329–333 (2003). https://doi.org/10.1023/A:1021935728607

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021935728607

Search

Navigation