Positive Correlation between nNOS and Stress-Activated Bowel Motility Is Confirmed by In Vivo HiBiT System

Han, Jeong Pil; Lee, Ju Han; Lee, Geon Seong; Koo, Ok Jae; Yeom, Su Cheong

doi:10.3390/cells10051028

Cited by 7 publications

(5 citation statements)

References 29 publications

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Section: Discussioncontrasting

confidence: 79%

“…The increased nNOS suggested the presence of more Cajal cells in CACS mice. Other studies have also shown that nNOS is positively correlated with irritable bowel motility ( Han et al, 2021 ). However, SNAP treatment had no significant effect on the expression of 5-HT or nNOS in CACS mice, which implied that neither 5-HT nor nNOS might be the mediator through which the LHA–BLA MCHergic neural pathway acts on the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 89%

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Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Zhang

et al. 2022

Front. Pharmacol.

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The limbic system plays a pivotal role in stress-induced anxiety and intestinal disorders, but how the functional circuits between nuclei within the limbic system are engaged in the processing is still unclear. In our study, the results of fluorescence gold retrograde tracing and fluorescence immunohistochemistry showed that the melanin-concentrating hormone (MCH) neurons of the lateral hypothalamic area (LHA) projected to the basolateral amygdala (BLA). Both chemogenetic activation of MCH neurons and microinjection of MCH into the BLA induced anxiety disorder in mice, which were reversed by intra-BLA microinjection of MCH receptor 1 (MCHR1) blocker SNAP-94847. In the chronic acute combining stress (CACS) stimulated mice, SNAP94847 administrated in the BLA ameliorated anxiety-like behaviors and improved intestinal dysfunction via reducing intestinal permeability and inflammation. In conclusion, MCHergic circuit from the LHA to the BLA participates in the regulation of anxiety-like behavior in mice, and this neural pathway is related to the intestinal dysfunction in CACS mice by regulating intestinal permeability and inflammation.

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Section: Discussioncontrasting

confidence: 79%

Section: Discussionmentioning

confidence: 89%

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Zhang

et al. 2022

Front. Pharmacol.

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“…The NO plays an important role in the regulation of intestinal motility. The formation of reactive oxygen species would produce an alteration in the NO bioavailability, leading to alterations in the intestinal motility [43,44,46,47]. This study showed that H. stoechas extract inhibit the content of MDA+4-HDA produced in the tissue treated with LPS, demonstrating the antioxidant activity of the H. stoechas extract.…”

Section: Mda+4-hda Contentmentioning

confidence: 55%

Involvement of NO/cGMP Signaling Pathway, Ca2+ and K+ Channels on Spasmolytic Effect of Everlasting Flower Polyphenolic Extract (Helichrysum stoechas (L.) Moench)

Valero

López

Castro

et al. 2022

IJMS

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Functional gastrointestinal diseases (FGID) are worldwide prevalent conditions. Pharmacological treatments can be ineffective, leading the population to turn to herbal or traditional remedies. Helichrysum stoechas (L.) Moench is a medicinal plant traditionally used in the Iberian Peninsula to treat digestive disorders, but its effects on gastrointestinal motility have not been scientifically demonstrated. The aim of this work was to evaluate the antispasmodic effect of a polyphenolic extract of H. stoechas (HSM), its mechanism of action and its antioxidant activity. Isometric myography studies were performed in rat ileum, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) levels were measured in rat jejunum. HSM reduced the integrated mechanical activity of spontaneous contractions. In Ca2+-free medium, HSM reduced the concentration–response curve of CaCl2 similarly to verapamil. Pre-incubation with the extract blocked the contraction induced by Bay K8644, KCl and carbachol. L-NAME, ODQ, Rp-8-Br-PET-cGMPS, KT-5823, apamin, TRAM-34 and charybdotoxin reduced the relaxant effect of the extract on spontaneous contractions. MDA+4-HDA levels in LPS-treated tissue were reduced by the extract, showing antioxidant activity. In conclusion, HSM showed antispasmodic activity through inhibition of Ca2+ influx, activation of the NO/PKG/cGMP pathway and opening of Ca2+-activated K+ channels. The results suggest that H. stoechas could help in the prevention or treatment of FGIDs.

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“…In addition, it was reported that a high expression level of nNOS in the brain and colon of IBS rats, whereas a positive correlation was found between nNOS expression and bowel motility in stress-induced IBS rats. [20]. Clinical studies have also reported increased NO production in plasma and rectal tissues of IBS patients [21,22].Collectively, these ndings suggest that the gut microbiota and nNOS are likely key factors regulating stress-induced IBS with visceral hypersentivity.…”

Section: Introductionmentioning

confidence: 76%

“…Previous studies have shown that nNOS is a key enzyme for the production of NO in central and peripheral nervous systems [40]. Han et al reported a signi cant increase in nNOS expression in organs of the large intestine, adrenal gland, and hypothalamus, as well as suggested that nNOS could be a biomarker of the HPA axis linked to visceral hypersensitivity in IBS [20]. The experimental results discussed herein showed that nNOS protein and mRNA levels increased signi cantly in IBS rat with visceral hypersensitivity, which was also accompanied by the imbalance of gut microbiota, as demonstrated by an increase in the abundance of pathogenic bacteria, such as Escherichia coli, as well as a decrease in the proportion of obligatory anaerobic bacteria, including butyrate-producing bacteria.…”

Section: Discussionmentioning

confidence: 99%

Effects of nNOS inhibition on the Escherichia coli and butyrate-producing bacteria in IBS rats with visceral hypersensitivity

Huang

Sun

et al. 2023

Preprint

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Background: Irritable bowel syndrome (IBS) is described as a disorder of the microbiota-gut-brain axis, with a distinguishing feature of visceral hypersensitivity. An imbalanced gut microbiota is closely related to the occurrence of IBS. Neuronal nitric oxide synthase (nNOS) may be an essential regulatory factor in stress-induced IBS. However, the relationship between gut microbiota and nNOS expression is still poorly understood. The aim of the present study is to investigate the effects of nNOS inhibition on the changes of Escherichia coli and butyrate-producing bacteria in IBS rats with visceral hypersensitivity. Method: Colorectal distention (CRD) combined with restraint stress (RS) was used to generate an IBS rat model with visceral hypersensitivity. L-NAME was administered as an nNOS inhibitor. Abdominal withdrawal reflex (AWR) test was used to evaluate visceral sensitivity in rats. Western blotting and real-time PCR were used to determine expression levels of nNOS in the distal colon of rats. The content of nitric oxide (NO) andnitritein the distal colon of rats was determined using colorimetric methods. Gut microbiota was assessed by fluorescence qPCR. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to quantify butyrate content in the feces and distal colon of rats. Results: nNOS inhibiton could attenuate visceral hypersensitivity in stress-induced IBS rats. Gut microbiota was changed after treatment with nNOS inhibiton, which was characterized by a decrease in the abundance of Escherichia coli and an increase in the abundance of butyrate-producing bacteria. Moreover, nNOS inhibiton decreased the contents of NO and nitrite and increased butyrate content in the distal colon of rats. From further Spearman’s correlation analysis, nNOS expression was positively correlated with Escherichia coliand negatively correlated with butyrate-producing bacteria. Conclusion: nNOS inhibiton reduced the production of NO and nitrite by down-regulation of expression levels of nNOS, thus regulating the imbalance of gut microbiota,as demonstrated by a decrease in the abundance of Escherichia coli, as well as an increase in the abundance of butyrate-producing bacteria, which contributed to attenuating the visceral hypersensitivity in IBS rats.

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Positive Correlation between nNOS and Stress-Activated Bowel Motility Is Confirmed by In Vivo HiBiT System

Cited by 7 publications

References 29 publications

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Involvement of NO/cGMP Signaling Pathway, Ca2+ and K+ Channels on Spasmolytic Effect of Everlasting Flower Polyphenolic Extract (Helichrysum stoechas (L.) Moench)

Effects of nNOS inhibition on the Escherichia coli and butyrate-producing bacteria in IBS rats with visceral hypersensitivity

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