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Stress and the Stomach: Corticotropin-Releasing Factor May Protect the Gastric Mucosa in Stress Through Involvement of Glucocorticoids

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Abstract

Stress may contribute to the development of gastric ulcer disease. The results of our previous investigations suggest that glucocorticoids released during acute stress act as gastroprotective hormones, and not as ulcerogenic agents as has been generally accepted for a long time. In this study, we investigated whether corticotropin-releasing factor (CRF) may protect the gastric mucosa against stress-induced gastric injury through involvement of glucocorticoids. Intraperitoneal administration of CRF (1.25 μg/kg, 30 min before stress) markedly increased plasma corticosterone level (at 15 and 30 min after the administration) and significantly suppressed the occurrence of gastric erosion induced by 3-h cold-restraint stress (at 10°C) in conscious rats. To test the participation of corticosterone in the gastroprotective effect of exogenous CRF, two approaches were used: pretreatment by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg, i.p.) and the antagonist of glucocorticoid receptors RU-38486 (20 mg/kg, i.p.). Metyrapone injected shortly before CRF administration caused a fast inhibition of CRF-induced corticosterone response and reversed the protective effect of CRF on the gastric mucosa against the stress-induced erosion. The gastroprotective effect of CRF was also attenuated by the pretreatment rats with glucocorticoid receptor antagonist RU-38486. The results suggest that exogenous CRF may protect the gastric mucosa against stress-induced gastric injury through involvement of glucocorticoids.

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References

  • Alexandrova M (1994) Stress induced tyrosine aminotransferase activity via glucocorticoid receptor. Horm Metab Res 26:97–99

    Article  PubMed  CAS  Google Scholar 

  • Bakke HK, Murison R (1989) Plasma corticosterone and restraint induced gastric pathology: age-related differences after administration of corticotropin releasing factor. Life Sci 45:907–916

    Article  PubMed  CAS  Google Scholar 

  • Bakke HK, Bogsnes A, Murison R (1990) Studies on the interaction between ICV effects of CRF and CNS noradrenaline depletion. Physiol Behav 47:1253–1260

    Article  PubMed  CAS  Google Scholar 

  • Filaretova L (1990) The dependence of the formation of stress gastric ulcers on the function of hypothalamo–hypophyseal–adrenocortical system. Sechenov Physiol J USSR 76:1594–1600

    CAS  Google Scholar 

  • Filaretova LP (2006) The hypothalamic–pituitary–adrenocortical system: hormonal brain–gut interaction and gastroprotection. Auton Neurosci 125:86–93

    Article  PubMed  CAS  Google Scholar 

  • Filaretova LP, Filaretov AA, Makara GB (1998) Corticosterone increase inhibits stress-induced gastric erosions in rats. Am J Physiol 274:G1024–G1030

    PubMed  CAS  Google Scholar 

  • Filaretova LP, Maltcev AN, Bogdanov AI, Levkovich YuI (1999) Role of gastric microcirculation in the gastroprotection by glucocorticoids released during water-restraint stress in rats. Chin J Physiol 42:145–152

    PubMed  CAS  Google Scholar 

  • Filaretova LP, Bagaeva TR, Makara GB (2002) Aggravation of nonsteroidal antiinflammatory drug gastropathy by glucocorticoid deficiency or blockade of glucocorticoid receptor in rats. Life Sci 71:2457–2468

    Article  PubMed  CAS  Google Scholar 

  • Filaretova LP, Podvigina TT, Bagaeva TR, Tanaka A, Takeuchi K (2004) Mechanisms underlying gastroprotective action of glucocorticoids released in response to ulcerogenic stress factors. Ann N Y Acad Sci 1018:288–293

    Article  PubMed  CAS  Google Scholar 

  • Filaretova L, Bagaeva T, Amagase K, Takeuchi K (2008) Contribution of glucocorticoids to protective influence of preconditioning mild stress against stress-induced gastric erosions. Ann N Y Acad Sci 1148:209–212

    Article  PubMed  CAS  Google Scholar 

  • Gabry KE, Chrousos GP, Rice KC, Mostafa RM, Sternberg E, Negrao AB, Webster EL, McCann SM, Gold PW (2002) Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs. Mol Psychiatry 7:474–483

    Article  PubMed  CAS  Google Scholar 

  • Garrick T, Veiseh A, Taché Y, Weiner H (1987) Corticotropin-releasing factor acts on the brain to reduce gastric contractility. Psychother Psychosom 48:14–20

    Article  PubMed  CAS  Google Scholar 

  • Gunion MW, Kauffman GL Jr, Taché Y (1990) Intrahypothalamic corticotropin-releasing factor elevates gastric bicarbonate and inhibits stress ulcers in rats. Am J Physiol 258:G152–G157

    PubMed  CAS  Google Scholar 

  • Jezova D, Ochedalski T, Glickman M, Kiss A, Aguilera G (1999) Central corticotropin-releasing hormone receptors modulate hypothalamic–pituitary–adrenocortical and sympathoadrenal activity during stress. Neuroscience 94:797–802

    Article  PubMed  CAS  Google Scholar 

  • Kawakubo K, Taché Y (1999) Protective effect of endogenous CRF on restraint-induced gastric lesions in rats. Gastroenterology 116:A210

    Article  Google Scholar 

  • Kvetnansky R, Sabban EL, Palkovits M (2009) Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 89:535–606

    Article  PubMed  CAS  Google Scholar 

  • Laine L, Takeuchi K, Tarnawski A (2008) Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 135:41–60

    Article  PubMed  CAS  Google Scholar 

  • Liu S, Ren W, Qu MH, Bishop GA, Wang GD, Wang XY, Xia Y, Wood JD (2010) Differential actions of urocortins on neurons of the myenteric division of the enteric nervous system in guinea pig distal colon. Br J Pharmacol 159:222–236

    Article  PubMed  CAS  Google Scholar 

  • Mikics E, Kruk MR, Haller J (2004) Genomic and non-genomic effects of glucocorticoids on aggressive behavior in male rats. Psychoneuroendocrinology 29:618–635

    Article  PubMed  CAS  Google Scholar 

  • Pavel J, Benicky J, Murakami Y, Sanchez-Lemus E, Saavedra JM (2008) Peripherally administered angiotensin II AT1 receptor antagonists are anti-stress compounds in vivo. Ann N Y Acad Sci 1148:360–366

    Article  PubMed  CAS  Google Scholar 

  • Ray A, Henke PG, Gulati K, Sen P (1993) The amygdaloid complex, corticotropin releasing factor and stress-induced gastric ulcerogenesis in rats. Brain Res 624:286–290

    Article  PubMed  CAS  Google Scholar 

  • Rivier CL, Grigoriadis DE, Rivier JE (2003) Role of corticotropin-releasing factor receptors type 1 and 2 in modulating the rat adrenocorticotropin response to stressors. Endocrinology 144:2396–2403

    Article  PubMed  CAS  Google Scholar 

  • Shibasaki T, Yamauchi N, Hotta M, Masuda A, Oono H, Wakabayashi I, Ling N, Demura H (1990) Brain corticotropin-releasing factor acts as inhibitor of stress-induced gastric erosion in rats. Life Sci 47:925–932

    Article  PubMed  CAS  Google Scholar 

  • Stengel A, Taché Y (2010) Corticotropin-releasing factor signaling and visceral response to stress. Exp Biol Med 235:1168–1178

    Article  CAS  Google Scholar 

  • Taché Y, Brunnhuber S (2008) From Hans Selye’s discovery of biological stress to the identification of corticotropin-releasing factor signaling pathways: implication in stress-related functional bowel diseases. Ann N Y Acad Sci 1148:29–41

    Article  PubMed  Google Scholar 

  • Taché Y, Goto Y, Gunion MW, Vale W, River J, Brown M (1983) Inhibition of gastric acid secretion in rats by intracerebral injection of corticotropin-releasing factor. Science 4626:935–937

    Article  Google Scholar 

  • Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotrophin and beta-endorphin. Science 213:1394–1397

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Cardin S, Martínez V, Taché Y (1996) Intracerebroventricular CRF inhibits cold restraint-induced c-fos expression in the dorsal motor nucleus of the vagus and gastric erosions in rats. Brain Res 736:44–53

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the grants of RFBR-10-04-00605; FNM RAS-2010-2011; DBS RAS-2011.

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Authors and Affiliations

  1. Laboratory of Experimental Endocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, nab. Makarova 6, St. Petersburg, Russia, 199034

    Ludmila Filaretova, Tatiana Bagaeva & Olga Morozova

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  1. Ludmila Filaretova
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  2. Tatiana Bagaeva
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  3. Olga Morozova
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Correspondence to Ludmila Filaretova.

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Filaretova, L., Bagaeva, T. & Morozova, O. Stress and the Stomach: Corticotropin-Releasing Factor May Protect the Gastric Mucosa in Stress Through Involvement of Glucocorticoids. Cell Mol Neurobiol 32, 829–836 (2012). https://doi.org/10.1007/s10571-012-9800-z

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  • DOI: https://doi.org/10.1007/s10571-012-9800-z

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