Corticotropin-Releasing
Hormone Receptor 1 Antagonist With or Without Corticotropin-Releasing Hormone Receptor 2
Remain Promising in Relieving Human Acute Psychological Stress and Related Intestinal
Hyperpermeability
Li-Yen
Tseng, Akio Inui, Chih-Yen Chen
Li-Yen
Tseng, Department of
Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Akio
Inui, Department of
Psychosomatic Internal Medicine, Kagoshima University Graduate School of
Medical and Dental Sciences, Kagoshima, Japan
Chih-Yen
Chen, Division of
Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, and
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei,
Taiwan
Correspondence
to: Chih-Yen Chen, Division of Gastroenterology, Department of Medicine,
Taipei Veterans General Hospital, and Faculty of Medicine, National Yang-Ming
University School of Medicine, Taipei, Taiwan.
Email: chency@vghtpe.gov.tw
Telephone: +886-228712121 ext: 3763 Fax:
+886-2-28711058
Received: March 21,
2015
Revised: May 15, 2015
Accepted: May 21, 2015
Published online: June 6, 2015
ABSTRACT
Corticotropin-releasing
hormone (CRH) has clinical relevant to stress, feeding behavior, gut motility
and immunity. Emerging evidence indicates that two CRH receptor subtypes,
receptor 1 (CRH1-R) and 2 (CRH2-R), play pivotal roles in the regulation of these
biological functions induced by CRH, depending on which receptor subtypes to be
activated. Manipulating and balancing at CRH1-R and CRH2-R has become a novel
concept to treat stress-related disorders and gut dysfunction, such as
psychological stress and related intestinal hyperpermeability.
© 2015 ACT. All
rights reserved.
Key words: Corticotropin-releasing hormone; Intestinal
hyperpermeability; Receptor; Stress
Tseng LY, Inui A,
Chen CY. Corticotropin-Releasing Hormone Receptor 1 Antagonist With or Without
Corticotropin-Releasing Hormone Receptor 2 Remain Promising in Relieving Human
Acute Psychological Stress and Related Intestinal Hyperpermeability. Journal of Biochemistry and Molecular Biology Research 2015; 1(2): 30-31
Available from: URL: http://www.ghrnet.org/index.php/jbmbr/article/view/1160
EDITORIAL
A recent interesting article by Vanuytsel et al[1]
(Vanuytsel et al, 2014) describing psychological stress and
corticotropin-releasing hormone (CRH) to increase intestinal permeability in
humans through a mast cell-dependent mechanism. The authors concluded that
public speech rather than electroshock induced intestinal hyperpermeability.
Although both public speech and electroshock increased State-Trait Anxiety
Inventory (STAI) score, only public speech but not electroshock stimulated the
increase of salivary cortisol level, which reflexes the activation of the
hypothalamic-pituitary-adrenal (HPA) axis. It is very interesting to know how
electroshock induced stress without affecting the HPA axis. We doubt that the
intensity of electroshock plays a role in this difference.
The authors
further demonstrated that public speech not only elicited stress, activated HPA
axis, but also increased intestinal permeability. In addition, intravenous
administration of CRH reproduced stress-induced increases in salivary cortisol
and intestinal permeability, but not STAI score. In this study, exogenous CRH
was used to mimic the stressful conditions. We are curious about why
intravenously-injected CRH stimulated HPA axis (salivary cortisol was
increased) without eliciting any anxiety in man. One of the explanations is
peripheral CRH does not mimic perfectly the psychological stress response and
that of central administration of CRH. In this paper, the authors did not
mention the plasma concentrations of adrenocorticotrophic hormone, i.e. the
downstream mediator of CRH and upstream of cortisol. The measurement of plasma
adrenocorticotrophic hormone can give us further information. The level of
salivary cortisol may reflect both cortisol and salivary secretary capacity,
but the latter of which may be affected by stress and sympathetic nervous system.
The results that the intestinal hyperpermeability, but not salivary
cortisol concentrations (and/or STAI score), induced by public speech and
exogenous CRH was blocked by mast cell stabilizer sodium cromoglycate, may
reveal the superiority of CRH receptor antagonists to mast cell blockers in
reversing central neuroendocrinlogical and peripheral gut mucosal barrier
dysfunctions (Chen et al[2], 2014). Neuropeptides tend to
produce different neurobiological actions depending on which receptor subtype they
activate. CRH receptor 1 (CRH1-R) antagonist has been shown to
attenuate hippocampal noradrenaline release, visceral perception,
adrenocorticotropic hormone release, and anxiety in a rodent model (Saito et
al[3], 2005). On the other hand, CRH receptor 2 (CRH2-R)
has been demonstrated to induce anxiolytic response via phosphorylation of the
transcription factor cAMP response element-binding protein (Creb) but not
activation of HPA (Kishimoto et al[4], 2000). Furthermore,
CRH1-R has been identified on the cell surface of human intestinal mucosal mast
cells, and CRH is reported to activate CD14+ cells to produce tumor
necrosis factor-α and induce endothelial barrier dysfunction (Song et al[5],
2013). Using respective agonists and/or antagonists of CRH1-R and
CRH2-R in exploring human acute psychological stress and related
alteration of intestinal permeability becomes a very intriguing topic.
conclusion
In conclusion, differentially nibbling CRH1-R and CRH2-R
remains promising for the management of human acute psychological stress and
related intestinal hyperpermeability. The collective evidence can provide
useful implications for the future treatment and functional gastrointestinal
disorders, such as irritable bowel syndrome.
Acknowledgements
The project was funded in part by an intramural grant from Taipei
Veterans General Hospital (VGH 94-030) and Yen Tjing Ling Medical Foundation
(CI-100-31), Taiwan.
CONFLICT OF INTERESTS
The Author has no conflicts of interest to declare.
REFERENCES
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Peer reviewer: Peer reviewer: Yan Teng,
Associate Professor, Genetic laboratory of Development and Diseases, Institute
of Biotechnology, AMMS, 20 Dongdajie Street, Beijing 100071, China.
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