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Dehydroepiandrosterone sulfate improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome.
Eur J Pharmacol 2019; 852:198-206EJ

Abstract

Stress-induced altered visceral sensation and impaired gut barrier play an important role in the pathophysiology of irritable bowel syndrome (IBS). These responses were demonstrated to be peripheral corticotropin-releasing factor (CRF) dependent and also mediated via proinflammatory cytokine in animal IBS model. Dehydroepiandrosterone sulfate (DHEA-S) is known to have anti-inflammatory properties by suppressing proinflammatory cytokine release. We hypothesized that DHEA-S improves stress-induced visceral changes and is beneficial for IBS treatment. We explored the effects of DHEA-S on lipopolysaccharide (LPS)- or repeated water avoidance stress (WAS)-induced visceral allodynia and increased colonic permeability (rat IBS models). The threshold of visceromotor response, i.e. abdominal muscle contractions induced by colonic balloon distention was electrophysiologically measured. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue. DHEA-S abolished visceral allodynia and colonic hyperpermeability induced by LPS in a dose-dependent manner. It also blocked repeated WAS- or peripheral injection of CRF-induced visceral changes. These effects by DHEA-S in LPS model were reversed by bicuculline, a γ-aminobutyric acid (GABA)A receptor antagonist, NG-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor, naloxone, an opioid receptor antagonist, or sulpiride, a dopamine D2 receptor antagonist. However, domperidone, a peripheral dopamine D2 receptor antagonist did not modify the effects. Peripheral injection of astressin2-B, a selective CRF receptor subtype 2 (CRF2) antagonist also reversed these effects. In conclusion, DHEA-S blocked stress-induced visceral changes via GABAA, NO, opioid, central dopamine D2 and peripheral CRF2 signaling. DHEA-S may be useful for IBS treating.

Authors+Show Affiliations

Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan. Electronic address: tnozu@sea.plala.or.jp.Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan. Electronic address: miyagishi@asahikawa-med.ac.jp.Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan. Electronic address: rintaro.1500@gmail.com.Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan. Electronic address: kusaki@asahikawa-med.ac.jp.Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan; Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan. Electronic address: okumurat@asahikawa-med.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30935894

Citation

Nozu, Tsukasa, et al. "Dehydroepiandrosterone Sulfate Improves Visceral Sensation and Gut Barrier in a Rat Model of Irritable Bowel Syndrome." European Journal of Pharmacology, vol. 852, 2019, pp. 198-206.
Nozu T, Miyagishi S, Nozu R, et al. Dehydroepiandrosterone sulfate improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome. Eur J Pharmacol. 2019;852:198-206.
Nozu, T., Miyagishi, S., Nozu, R., Takakusaki, K., & Okumura, T. (2019). Dehydroepiandrosterone sulfate improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome. European Journal of Pharmacology, 852, pp. 198-206. doi:10.1016/j.ejphar.2019.03.037.
Nozu T, et al. Dehydroepiandrosterone Sulfate Improves Visceral Sensation and Gut Barrier in a Rat Model of Irritable Bowel Syndrome. Eur J Pharmacol. 2019 Jun 5;852:198-206. PubMed PMID: 30935894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dehydroepiandrosterone sulfate improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome. AU - Nozu,Tsukasa, AU - Miyagishi,Saori, AU - Nozu,Rintaro, AU - Takakusaki,Kaoru, AU - Okumura,Toshikatsu, Y1 - 2019/03/29/ PY - 2018/12/20/received PY - 2019/03/15/revised PY - 2019/03/22/accepted PY - 2019/4/3/pubmed PY - 2019/4/3/medline PY - 2019/4/3/entrez KW - Dehydroepiandrosterone sulfate KW - Gut barrier KW - Irritable bowel syndrome KW - Visceral pain SP - 198 EP - 206 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 852 N2 - Stress-induced altered visceral sensation and impaired gut barrier play an important role in the pathophysiology of irritable bowel syndrome (IBS). These responses were demonstrated to be peripheral corticotropin-releasing factor (CRF) dependent and also mediated via proinflammatory cytokine in animal IBS model. Dehydroepiandrosterone sulfate (DHEA-S) is known to have anti-inflammatory properties by suppressing proinflammatory cytokine release. We hypothesized that DHEA-S improves stress-induced visceral changes and is beneficial for IBS treatment. We explored the effects of DHEA-S on lipopolysaccharide (LPS)- or repeated water avoidance stress (WAS)-induced visceral allodynia and increased colonic permeability (rat IBS models). The threshold of visceromotor response, i.e. abdominal muscle contractions induced by colonic balloon distention was electrophysiologically measured. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue. DHEA-S abolished visceral allodynia and colonic hyperpermeability induced by LPS in a dose-dependent manner. It also blocked repeated WAS- or peripheral injection of CRF-induced visceral changes. These effects by DHEA-S in LPS model were reversed by bicuculline, a γ-aminobutyric acid (GABA)A receptor antagonist, NG-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor, naloxone, an opioid receptor antagonist, or sulpiride, a dopamine D2 receptor antagonist. However, domperidone, a peripheral dopamine D2 receptor antagonist did not modify the effects. Peripheral injection of astressin2-B, a selective CRF receptor subtype 2 (CRF2) antagonist also reversed these effects. In conclusion, DHEA-S blocked stress-induced visceral changes via GABAA, NO, opioid, central dopamine D2 and peripheral CRF2 signaling. DHEA-S may be useful for IBS treating. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/30935894/Dehydroepiandrosterone_sulfate_improves_visceral_sensation_and_gut_barrier_in_a_rat_model_of_irritable_bowel_syndrome L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(19)30198-0 DB - PRIME DP - Unbound Medicine ER -