Skip to main content
Log in

Involvement of Hypothalamo-Hypophyseal-Adrenocortical System Hormones in Gastroprotection in Rats on Sensitization and Desensitization of Capsaicin-Sensitive Afferent Neurons

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

The aims of the present work were: a) to study the contribution of glucocorticoid hormones to gastroprotection induced by sensitization of capsaicin-sensitive afferent neurons (CSN); b) to study the gastroprotective effect of corticotropin-releasing factor (CRF) in conditions of desensitization of CSN and the possible involvement of corticosterone in this effect. Experiments were run using male Sprague–Dawley rats weighing 260–300 g. Ulcerogenic stimuli consisted of immobilization at 10°C (3 h) or administration of indomethacin at a dose of 35 mg/kg. Sensitization of CSN was by administration of capsaicin at doses of 1 and 10 mg/kg 1 h before presentation of ulcerogenic stimuli and desensitization was by administration of capsaicin to a total neurotoxic dose of 100 mg/kg (20 + 30 + 50) on three sequential days two weeks before experiments started. CRF was given i.p. at a dose of 2.5 mg/kg 30 min before administration of indomethacin to rats with desensitization of CSN. Studies of the involvement of corticosterone in the gastroprotective effects used its synthesis inhibitor metyrapone at a dose of 30 mg/kg. Capsaicin given at doses of 1 and 10 mg/kg induced gastroprotective effects in both ulcerogenesis models. Administration of metyrapone 30 min before capsaicin prevented the gastroprotective effect of CSN sensitization induced by administration of capsaicin at a dose of 1 mg/kg, but has no effect on the gastroprotective effect of capsaicin at a dose of 10 mg/kg. Administration of CRF induced a gastroprotective effect not only in control rats, but also in animals with desensitization of CSN. The results of experiments with metyrapone provided evidence that the gastroprotective effect of CRF seen here in rats with desensitization of CSN was at least partially mediated by corticosterone.

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.

Similar content being viewed by others

References

  1. J. Szolcsanyi and L. Bartho, “Capsaicin-sensitive afferents and their role in gastroprotection: an update,” J. Physiol. (Paris), 95, No. 1–6, 181–188 (2001).

    Article  CAS  Google Scholar 

  2. P. Holzer, “Efferent-like roles of afferent neurons in the gut: blood flow regulation and tissue protection,” Auton. Neurosci., 125, No. 1–2, 70–75 (2006).

    Article  Google Scholar 

  3. N. Harada and K. Okajima, “Inhibition of neutrophil activation by lafutidine, an H2-receptor antagonist, through enhancement of sensory neuron activation contributes to the reduction of stress-induced gastric mucosal injury in rats,” Dig. Dis. Sci., 52, No. 2, 469–477 (2007).

    Article  CAS  Google Scholar 

  4. S. Kwiecien, K. Magierowska, M. Magierowski, et al., “Role of sensory afferent nerves, lipid peroxidation and antioxidative enzymes in the carbon monoxide-induced gastroprotection against stress ulcerogenesis,” J. Physiol. Pharmacol., 67, No. 5, 717–729 (2016).

    CAS  PubMed  Google Scholar 

  5. G. Mozsik, “Capsaicin as new orally applicable gastroprotective and therapeutic drug alone or in combination with nonsteroidal anti-inflammatory drugs in healthy human subjects and in patients,” Prog. Drug Res., 68, 209–258 (2014).

    CAS  PubMed  Google Scholar 

  6. P. Yu. Bobryshev, T. T. Podvigina, T. R. Bagaeva, and L. P. Filaretova, “Compensatory gastroprotective action of glucocorticoid hormones in the rats with inactivation of the functions of capsaicin-sensitive neurons,” Ros. Fiziol. Zh., 92, No. 8, 1006–1015 (2006).

    CAS  Google Scholar 

  7. G. Mozsik, A. Vincze, and J. Szolcsanyi, “Four response stages of capsaicin-sensitive primary afferent neurons to capsaicin and its analog: gastric acid secretion, gastric mucosal damage and protection,” J. Gastroenterol. Hepatol., 16, No. 10, 1093–1097 (2001).

    Article  CAS  Google Scholar 

  8. L. Filaretova, P. Bobryshev, T. Bagaeva, et al., “Compensatory gastroprotective role of glucocorticoid hormones during inhibition of prostaglandin and nitric oxide production and desensitization of capsaicin-sensitive neurons,” Inflammopharmacology, 15, No. 4, 146–153 (2007).

  9. L. P. Filaretova and N. I. Yarushkina, “Capsaicin-sensitive neurons: role in gastroprotection and the regulation of pain sensitivity,” Usp. Fiziol. Nauk., 50, No. 1, 3–16 (2019).

    Google Scholar 

  10. P. Holzer, “Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system,” Pharmacol. Ther., 131, No. 1, 142–170 (2011).

    Article  CAS  Google Scholar 

  11. D. A. Kunde, J. Yingchoncharoen, S. Jurković, and D. P. Geraghty, “TRPV1 mediates capsaicin-stimulated metabolic activity but not cell death or inhibition of interleukin-1β release in human THP-1 monocytes,” Toxicol. Appl. Pharmacol., 360, 9–17 (2018), https://doi.org/10.1016/j.taap.2018.

    Article  CAS  PubMed  Google Scholar 

  12. P. C. Konturek, T. Brzozowski, B. Walter, et al., “Ghrelin-induced gastroprotection against ischemia-reperfusion injury involves an activation of sensory afferent nerves and hyperemia mediated by nitric oxide,” Eur. J. Pharmacol., 536, No. 1–2, 171–181 (2006).

    Article  CAS  Google Scholar 

  13. F. Sun, S. Xiong, and Z. Zhu, “Dietary capsaicin protects cardio metabolic organs from dysfunction,” Nutrients, 8, No. 5, E174 (2016), https://doi.org/10.3390/nu8050174.

  14. K. Takeuchi, S. Kato, M. Takeeda, et al., “Facilitation by endogenous prostaglandins of capsaicin-induced protection in rodent through EP2 and IP receptors,” J. Pharmacol. Exp. Ther., 304, No. 3, 1055–1062 (2003).

    Article  CAS  Google Scholar 

  15. D. Garabadu, A. Shah, A. Ahmad, et al., “Eugenol as an anti-stress agent: modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress,” Stress, 14, No. 2, 145–155 (2011).

  16. J. Martinek, K. Hlavova, F. Zavada, et al., “’A surviving myth’ – corticosteroids are still considered ulcerogenic by a majority of physicians,” Scand. J. Gastroenterol., 45, No. 10, 1156–1161 (2010).

    Article  Google Scholar 

  17. L. P. Filaretova, A. A. Filaretov, and G. B. Makara, “Corticosterone increase inhibits stress-induced gastric erosions in rats,” Am. J. Physiol., 274, No. 6, G1024–G1030 (1998).

    CAS  PubMed  Google Scholar 

  18. L. P. Filaretova, “Contribution of glucocorticoid hormones to gastroprotection,” Usp. Fiziol. Nauk., 45, No. 1, 43–55 (2014).

    Google Scholar 

  19. L. Filaretova, T. Bagaeva, and O. Morozova, “Stress and stomach: corticotropin-releasing factor may protect the gastric mucosa through involvement of glucocorticoids,” Cell. Mol. Neurobiol., 32, No. 5, 829–836 (2012).

    Article  CAS  Google Scholar 

  20. L. Filaretova, T. Podvigina, and N. Yaryshkina, “Physiological and pharmacological effects of glucocorticoids on the gastrointestinal tract,” Curr. Pharm. Des., 26, No. 25, 2962–2970 (2020), https://doi.org/10.2174/1381612826666200521142746.

    Article  CAS  PubMed  Google Scholar 

  21. L. Filaretova, T. Podvigina, T. Bagaeva, and O. Morozova, “From gastroprotective to ulcerogenic effects of glucocorticoids: role of long-term glucocorticoid action,” Curr. Pharm. Des., 20, No. 7, 1045–1050 (2014).

    Article  CAS  Google Scholar 

  22. T. T. Podvigina, P. Y. Bobryshev, T. R. Bagaeva, et al., “The effects of desensitization of capsaicin-sensitive afferent neurons on the microcirculation in the stomach in rats depend on the blood glucocorticoid hormone level,” Neurosci. Behav. Physiol., 39, No. 6, 559–564 (2009).

    Article  CAS  Google Scholar 

  23. A. E. Morgan and C. H. Lang, “Involvement of capsaicin-sensitive nerves in regulating the hormone and glucose metabolic response to endotoxin,” Am. J. Physiol., 273, No. 2, Pt 1, E328–E335 (1997).

  24. T. T. Podvigina, O. Yu. Morozova, S. D. Solnushkin, et al., “Effects of sensitization and desensitization of capsaicin-sensitive neurons on the formation of gastric mucosal erosions induced by indomethacin in rats: the role of glucocorticoid hormones,” Ros. Fiziol. Zh., 105, No. 2, 225–237 (2019).

    Article  Google Scholar 

  25. L. Filaretova and T. Bagaeva, “The realization of the brain-gut interactions with corticotropin releasing factor and glucocorticoids,” Curr. Neuropharmacol., 14, No. 8, 876–881 (2016).

    Article  CAS  Google Scholar 

  26. L. P. Filaretova, “Contribution of corticotropin-releasing factor to gastroprotection,” Neirokhimiya, 35, No. 2, 122–125 (2018).

  27. T. T. Podvigina, O. Yu. Morozova, T. R. Bagaeva, and L. P. Filaretova, “Gastroprotective effect of corticotropin-releasing factor in rats with streptozotocin-induced diabetes,” Ros. Fiziol. Zh., 102, No. 11, 1352–1362 (2016).

    CAS  Google Scholar 

  28. S. D. Solnushkin and V. N. Chikhman, “Computer processing of biological images,” Biomed. Radioelektronika, 2, 35–40 (2018).

    Google Scholar 

  29. M. I. Cordero, N. D. Kruyt, J. J. Merino, and C. Sandi, “Glucocorticoid involvement in memory formation in a rat model for traumatic memory,” Stress, 5, No. 1, 73–79 (2002).

  30. S. R. Bloom, A. V. Edwards, and C. T. Jones, “Adrenal responses to calcitonin gene-related peptide in conscious hypophysectomized calves,” J. Physiol., 409, 29–41 (1989).

    Article  CAS  Google Scholar 

  31. Y. J. Choi, J. Y. Kim, S. B. Yoo, et al., “Repeated oral administration of capsaicin increases anxiety-like behaviors with prolonged stress-response in rats,” J. Biosci, 38, No. 3, 561–571 (2013).

    Article  CAS  Google Scholar 

  32. L. G. Ferreira, J. P. Prevatto, H. R. Freitas, et al., “Capsaicin inhibits lipopolysaccharide-induced adrenal steroidogenesis by raising intracellular calcium levels,” Endocrine, 64, No. 1, 169–175 (2019).

  33. J. Donnerer and F. Lembeck, “Different control of the adrenocorticotropin-corticosterone response and of prolactin secretion during cold stress, anesthesia, surgery, and nicotine injection in the rat: involvement of capsaicin-sensitive sensory neurons,” Endocrinology, 126, No. 2, 921–926 (1990).

  34. T. Watanabe, A. Morimoto, N. Tan, et al., “ACTH response induced in capsaicin-desensitized rats by intravenous injection of interleukin-1 or prostaglandin,” Eur. J. Physiol., 475, No. 1, 139–145 (1994).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. T. Podvigina.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 106, No. 11, 1385–1399, November, 2020.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Podvigina, T.T., Morozova, O.Y., Komkova, O.P. et al. Involvement of Hypothalamo-Hypophyseal-Adrenocortical System Hormones in Gastroprotection in Rats on Sensitization and Desensitization of Capsaicin-Sensitive Afferent Neurons. Neurosci Behav Physi 51, 784–792 (2021). https://doi.org/10.1007/s11055-021-01135-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-021-01135-w

Keywords

Navigation