Upregulation of Gastric Norepinephrine With β-Adrenoceptors and Gastric Dysmotility in a Rat Model of Functional Dyspepsia

Jin, Song; Wang, T; Zhang, X; Li, B; Zhu, Congmin; Zhang, S

doi:10.33549/physiolres.934169

Cited by 7 publications

(3 citation statements)

References 29 publications

(27 reference statements)

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“…Dysmotility in FD is associated with an imbalance in the ENS. 32 YKS is not effective in improving abnormal movements, indicating that its efficacy is limited in the ENS. In contrast, RKT was effective against dysmotility in FD via enhancement of ghrelin secretion.…”

Section: Discussionmentioning

confidence: 99%

Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia

Duan

Imamura

Kondo

et al. 2022

J Neurogastroenterol Motil

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Background/AimsHerbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation. MethodsThe MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. After YKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 in the spinal cord was performed. ResultsYKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord. In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility. ConclusionsYKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract. This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.

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Section: Discussionmentioning

confidence: 99%

Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia

Duan

Imamura

Kondo

et al. 2022

J Neurogastroenterol Motil

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“… 66 High norepinephrine levels may lead to gastric motility disorders. 67 This might explain why paroxetine is more likely to cause gastrointestinal side effects than citalopram.…”

Section: Discussionmentioning

confidence: 99%

Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis

Wang¹,

Li²,

Kang³

et al. 2022

TCRM

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Purpose Selective serotonin reuptake inhibitors (SSRIs) are the preferred treatments for depression. The most common adverse drug reactions are symptoms involving the digestive system, leading to low compliance in patients with depression. Therefore, it is important to assess the safety of SSRIs with respect to the digestive system. Several meta-analyses have compared the risks of digestive side effects of SSRIs and other antidepressants. We aimed to compare the risks of various SSRIs (fluoxetine, escitalopram, citalopram, paroxetine, and sertraline) for adverse reactions of the digestive system. Methods Systematic searches returned 30 randomized controlled trials (n = 5004) of five antidepressants and placebos. Results Fluoxetine had the lowest probability of digestive side effects, ranking fifth at 0.548. Sertraline had the highest probability of digestive side effects, with a probability of 0.611. For gastrointestinal tolerability, escitalopram was better than paroxetine (odds ratio [OR] =0.62, 95% confidence interval [CI] 0.43–0.87) and sertraline (OR=0.56, 95% CI 0.32–0.99). Conclusion Fluoxetine exhibited distinct advantages compared to other SSRIs, while sertraline had the greatest likelihood of digestive system side effects. These findings will help doctors understand the relative advantages of various antidepressants.

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“…For example, n-butanol fraction extracted from taraxacum officinale enhanced the contraction of both fundus and antrum to increase the intra-gastric pressure and lead to accelerated gastric emptying [50]. In another study, the enhanced expression of β-adrenoceptors and norepinephrine transporter in the corpus of rat with functional dyspepsia contributes to the delayed gastric emptying [51]. Our experiment found that the expression of CaSR in the myenteric plexus of gastric antrum was higher than that in the gastric corpus.…”

Section: Discussionmentioning

confidence: 99%

Effect of Calcium-Sensitive Receptor Agonist R568 on Gastric Motility and the Underlying Mechanism

et al. 2022

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Introduction: Calcium-sensitive receptor (CaSR) is expressed in the enteric nervous system of gastrointestinal tract. However, its role in the regulation of gastrointestinal motility has not yet been fully elucidated. We aimed to investigate the effect of the CaSR agonist - R568 on gastric motility and its potential mechanism. Methods: In vivo, R568 was given by gavage to explore gastric emptying with or without capsaicin which specifically blocks the function of vagal afferents; neurotransmitters synthetized in the myenteric plexus of the gastric corpus and antrum were analysed by ELISA and immunofluorescence staining; gastric muscle strips contraction recording and intracellular single unit firing recording were used to study the effect of R568 on muscle stirps and myenteric interstitial cells of Cajal (ICCs) ex vitro. Results: Gastric emptying was inhibited by R568 in Kunming male mice, and capsaicin weakened this effect. The expression of c-fos positive neurons increased in the nucleus tractus solitarius when R568 was treated. R568 decreased the expression of cholinergic neurons and reduced the synthesis of acetylcholine. Conversely, R568 increased the expression of nitrogenic neurons and enhanced the synthesis of nitric oxide in the myenteric plexus. Ex vitro results showed that R568 inhibited the contraction of the gastric antral muscle strip and suppressed the spontaneous firing activity of pacemaker ICCs. Conclusion: Activation of the gastrointestinal CaSR inhibited gastric motility in vivo and ex vitro. Transmitting nutrients signals to the brain through the vagal afferent nerve, modulating the cholinergic and nitrergic system in the enteric nervous system, and inhibiting activity of pacemaker ICCs in the myenteric plexus are involved in the mechanism of CaSR in gastric motility suppression.

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Upregulation of Gastric Norepinephrine With β-Adrenoceptors and Gastric Dysmotility in a Rat Model of Functional Dyspepsia

Cited by 7 publications

References 29 publications

Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia

Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia

Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis

Effect of Calcium-Sensitive Receptor Agonist R568 on Gastric Motility and the Underlying Mechanism

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