Effect of phosphodiesterase‐4 inhibitor rolipram on colonic hypermotility in water avoidance stress rat model

Yuan, Fangting; Ren, Haixia; Tan, Wei; Wáng, Ying; Luo, Hesheng

doi:10.1111/nmo.14317

Cited by 8 publications

(3 citation statements)

References 53 publications

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“…Previous studies have reported that the PDE4 inhibitors, rolipram and roflumilast, produced a dose-related inhibition of stress-induced increased fecal pellet output in vivo in animals ( Barone et al, 2008 ; Yuan et al, 2022 ). Moreover, high concentrations of rolipram (higher than 10 –5 M) inhibited the spontaneous contraction of colonic smooth muscle strips in vitro , and this inhibitory effect was partly through the cAMP–-PKA-p-CREB pathway and NO pathway ( Yuan et al, 2022 ). In the present study, the PDE4 inhibitor drotaverine did not affect the spontaneous activity of the smooth muscle.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of the mechanism of action of paracetamol, drotaverine, and peppermint oil and their effects in combination with hyoscine butylbromide on colonic motility: human ex-vivo study

Traserra,

Barber,

Alcalá-González

et al. 2024

Front. Pharmacol.

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IntroductionDrotaverine, paracetamol, and peppermint oil are often prescribed for the treatment of gastrointestinal spasm and pain. This study aimed to evaluate the effect of these drugs alone and combined with the well-known antispasmodic hyoscine butylbromide on the human colon.MethodsColon samples were obtained from macroscopically normal regions of 68 patients undergoing surgery and studied in muscle bath. Drotaverine, paracetamol, and peppermint oil were tested alone and in combination with hyoscine butylbromide on (1) spontaneous contractility induced by isometric stretch (in the presence of 1 µM tetrodotoxin) and (2) contractility induced by 10–5 M carbachol and after (3) electrical field stimulation-induced selective stimulation of excitatory (in the presence of 1 mM Nω-nitro-L-arginine and 10 µM MRS2179) and (4) inhibitory (under non-adrenergic, non-cholinergic conditions) pathways. (5) Drotaverine alone was also tested on cAMP-dependent pathway activated by forskolin.ResultsCompared with the vehicle, drotaverine and paracetamol (10−9–10−5 M) did not modify spontaneous contractions, carbachol-induced contractions, and responses attributed to selective activation of excitatory pathways. The addition of hyoscine butylbromide (10−7–10−5 M), concentration-dependently reduced myogenic contractions and carbachol- and electrical field stimulation-induced contractile responses. The association of paracetamol (10−4 M) and hyoscine butylbromide (10−7–10−5 M) was not different from hyoscine butylbromide alone (10−7–10−5 M). At higher concentrations (10−3M–3*10−3 M), paracetamol decreased myogenic and carbachol-induced contractions. The adenylate cyclase activator, forskolin, concentration-dependently reduced contractility, leading to smooth muscle relaxation. The effect of forskolin 10–7 M was concentration-dependently enhanced by drotaverine (10−6M–10−5M).DiscussionPeppermint oil reduced myogenic activity and carbachol- and electrical field stimulation-induced contractions. The association of hyoscine butylbromide and peppermint oil was synergistic since the interaction index measured with the isobologram was lower than 1. No effect was seen on the neural-mediated inhibitory responses with any of the drugs studied although peppermint oil reduced the subsequent off-contraction. Drotaverine and hyoscine butylbromide have a complementary effect on human colon motility as one stimulates the cAMP inhibitory pathway and the other inhibits the excitatory pathway. Peppermint oil is synergic with hyoscine butylbromide suggesting that a combination therapy may be more effective in treating patients. In contrast, at therapeutic concentrations, paracetamol does not modify colonic contractility, suggesting that the association of paracetamol and hyoscine butylbromide has independent analgesic and antispasmodic properties.

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Section: Discussionmentioning

confidence: 97%

Evaluation of the mechanism of action of paracetamol, drotaverine, and peppermint oil and their effects in combination with hyoscine butylbromide on colonic motility: human ex-vivo study

Traserra,

Barber,

Alcalá-González

et al. 2024

Front. Pharmacol.

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“…The NO is a potent smooth muscle relaxant and relaxes all the smooth muscles in the body [ 6 , 16 - 17 ]. There is ample evidence to suggest the involvement of nitric oxide in regulating intestinal contractility [ 6 , 18 - 19 ]. A recent study claimed that BPA caused a significant inhibition of duodenal movement by involving NO [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats

Dixit,

Roy,

Shukla

et al. 2024

Cureus

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Introduction Exposure to bisphenol A (BPA), a toxic chemical released from plastic, affects various body functions, including reproduction, metabolism, and development. The most common route of exposure to BPA is oral, and the gastrointestinal (GI) tract is, therefore, the first body system to be exposed to BPA. BPA has been well-documented to impair gut contractility in rats, in vitro. It may therefore be hypothesized that BPA may adversely affect GI motility and hence slow down the movement of food, resulting in the increased transit of food bolus in the GI tract. There are no reports so far on the effects of BPA on GI transit time. Objectives The present study was undertaken to examine the impact of exposure to BPA by a single oral dose (termed as short-term ingestion of BPA) and chronic (28-day) oral dose (termed as long-term ingestion of BPA) on the transit time of food bolus in the gut of adult male albino rats. Methods and materials The study was conducted in the Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. In one set of experiments, each animal was fed a food pellet, once (short-term ingestion) containing BPA (2 µg/kg and 50 µg/kg in different groups), and in another set of experiments, each animal was fed a food pellet containing BPA (50 µg/kg/day) for 28 consecutive days (long-term ingestion). Control rats in both sets were fed food pellets without BPA. Subsequently, the gastric transit index (GTI), ileocecal transit index (ICTI), and colonic transit time (CTT) were determined by the standard charcoal marker method. Results One-time ingestion of a food pellet containing BPA caused a significant (p < 0.05) drop in the GTI and ICTI and an increase in the CTT with both doses of BPA (2 and 50 µg/kg). Similarly, after chronic (28-day), oral BPA exposure, a significant decrease in the GTI and ICTT and an increase in CTT were observed. Conclusion Both short-term (one-time) and long-term (28-day) oral exposure to BPA-containing food harmed GI transit. Slow GI transit may lead to metabolic disorders and GI motility disorders, such as constipation.

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“…PDEs constitute a large family of enzymes that catalyze the degradation of cAMP and/or cGMP, and are important in modulating the intracellular concentrations of the cyclic nucleotides and in controlling their downstream signal transduction, involving cAMP-response element-binding protein (CREB) and NF-κB (Yuan et al, 2022;Chinn et al, 2022). PDE4B has attracted more attention because of its close relationship with inflammatory disease (Amata et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Suppression of cell pyroptosis by omeprazole through PDE4-mediated autophagy in gastric epithelial cells

YE,

SUN,

LIANG

et al. 2023

BIOCELL

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Introduction: Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction. Omeprazole was widely known as the first-line regimen for H. pylori-associated gastritis. Objectives: The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy. Methods: The clinical samples were collected. Quantitative polymerase chain reaction, western blotting, enzyme linked immunosorbent assay, and immunofluorescence (IF) analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy. Results: The results revealed that omeprazole could decrease cell pyroptosis, which was attributed to the downregulation of cleaved caspase-1 expression, resulting in the inhibition of gasdermin E and interleukin-18/1β maturation and secretion as well as the resolution of inflammation. Mechanistically, omeprazole treatment led to drastic downregulation of mammalian target of rapamycin (mTOR) activity was observed in BGC823 cells, leading to enhanced autophagy characterized by increased LC3II expression, which further reduced cell pyroptosis. This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4 (PDE4) inhibitor dipyridamole (DIP) treatment. In addition, activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole. Most importantly, IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H. pylori-infected gastric mucosa. Conclusion: These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells, and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis, implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H. pylori infection.

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Effect of phosphodiesterase‐4 inhibitor rolipram on colonic hypermotility in water avoidance stress rat model

Cited by 8 publications

References 53 publications

Evaluation of the mechanism of action of paracetamol, drotaverine, and peppermint oil and their effects in combination with hyoscine butylbromide on colonic motility: human ex-vivo study

Evaluation of the mechanism of action of paracetamol, drotaverine, and peppermint oil and their effects in combination with hyoscine butylbromide on colonic motility: human ex-vivo study

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats

Suppression of cell pyroptosis by omeprazole through PDE4-mediated autophagy in gastric epithelial cells

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