<i>In vitro</i>effect of pantoprazole on lower esophageal sphincter tone in rats

Duman, Mustafa; Özer, Mahmut; Reyhan, Enver; Demırcı, Yeliz; Atici, Ali Emre; Dalgıç, Tahsin; Bostancı, Erdal Birol; Genç, Ece

doi:10.3748/wjg.v17.i46.5105

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…In adult rodents PPIs induce a decrease in LES muscle tone in vitro (10,34). The PPI-induced reduction in LES tone is not unique to gastroesophageal muscle, since these compounds have been shown to relax all smooth muscle preparations where their effect was evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…Gastric fundus and LES smooth muscle mechanical response. Gastric longitudinally oriented fundic, or circular LES muscle strips (average 2 mm long and 5 mm wide) were studied via a modified protocol based on previous reports by others (8,10). The tissue mucosa and submucosa layers were carefully removed by sharp dissection and particular care taken with the newborn and juvenile strips to avoid damage to the underlying muscle layer.…”

Section: Methodsmentioning

confidence: 99%

“…Gastroesophageal reflux is commonly observed in neonates and particularly concerning in preterm infants since its occurrence has been associated with lung aspiration of gastric content and apnea (6). Studies conducted in adult animals have shown that PPIs reduce the lower esophageal sphincter (LES) muscle tone (10,34). The mechanism accounting for the in vitro PPIs' relaxant effect on gastroesophageal muscle contraction is presently unknown but unrelated to a number of key pathways involved in smooth muscle relaxation (1,12,21,23,33).…”

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confidence: 99%

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Pantoprazole decreases gastroesophageal muscle tone in newborn rats via rho-kinase inhibition

Welsh

Kasirer

Pan

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Proton pump inhibitors reduce gastric acid secretion and are commonly utilized in the management of gastroesophageal reflux disease across all ages. Yet a decrease in lower esophageal sphincter tone has been reported in vitro in rats through an unknown mechanism; however, their effect on the gastroesophageal muscle tone early in life was never studied. Hypothesizing that proton pump inhibitors also reduce gastroesophageal muscle contraction in newborn and juvenile rats, we evaluated the in vitro effect of pantoprazole on gastric and lower esophageal sphincter muscle tissue. Electrical field stimulation and carbachol-induced force were significantly (P < 0.01) reduced in the presence of pantoprazole, whereas the drug had no effect on the neuromuscular-dependent relaxation. When administered in vivo, pantoprazole (9 mg/kg) significantly (P < 0.01) reduced gastric emptying time at both ages. To ascertain the signal transduction pathway responsible for the reduction in muscle contraction, we evaluated the tissue ROCK-2 and CPI-17 activity. Pantoprazole reduced myosin light chain phosphatase MYPT-1, but not CPI-17 phosphorylation of gastric and lower esophageal sphincter tissue, strongly suggesting that it is a ROCK-2 inhibitor. To the extent that these findings can be extrapolated to human neonates, the use of pantoprazole may impair gastric and lower sphincter muscle tone and thus paradoxically exacerbate esophageal reflux. Further studies addressing the effect of proton pump inhibitors on gastroesophageal muscle contraction are warranted to justify its therapeutic use in gastroesophageal reflux disease.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Pantoprazole decreases gastroesophageal muscle tone in newborn rats via rho-kinase inhibition

Welsh

Kasirer

Pan

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…GERD conventional therapy involves the use of anti-secretory drugs such as proton pump inhibitors (PPI) and H2 receptor antagonists (HsRA) [16,17]. Despite of PPI efficacy to treat GERD, there is still a substantial group of cases (≈40% in some studies) who do not experience symptom relief with a standard PPI dose, due to transient lower esophageal sphincter relaxations, sensitivity to weakly acidic and/ or alkaline reflux, large volume of reflux and/or esophageal hypersensitivity [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Combined Therapy Effect of D-002 and Omeprazole on Chronic Esophagitis Induced by Duodenal Reflux in Rats

Zamora¹,

Mena²,

Molina³

et al. 2018

Journal of Gastroenterology and Metabolism

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Gastroesophageal reflux disease is a common gastrointestinal disorder. D-002 (beeswax alcohols) and omeprazole (OMP) present protective effects on esophagitis by reflux. In this study, the effect of combined therapy D002 + OMP on duodenum-esophageal reflux (DER) induced-esophagitis in rats was evaluated. Rats were randomized into five groups: one negative control and fourth groups with DER, including a positive control, two with D-002 and OMP (200 and 20 mg/kg, respectively), and other with combination therapy D-002 + OMP (200 + 20 mg/kg, respectively). All treatments were orally administered for 14 days after DER. Esophageal lesions' index (ELI), Histological score (HS) and malondialdehyde (MDA) content in esophagus were determined. Positive controls exhibited increase ELI, HS and MDA in esophagus compared to negative controls. The combination therapy lowered significantly both ELI (48.05%) and MDA (67.8%) compared to positive controls, but without significant differences compared to their respective monotherapies. However, the combination therapy significantly reduced the HS respect to the positive control, reaching 96% inhibition, an effect that was higher than each of the monotherapies. In conclusion, the administration of the combination therapy (D-002 + OMP) represents an additional benefit in the protection of esophageal tissue with respect to treatment with monotherapies.

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“…Longitudinally oriented gastric fundic, or circular LES, antral, ileal, and descending colon muscle strips (2 mm long and 5 mm wide) were studied using a modified protocol based on previous reports by others (35,36). The tissue mucosa and submucosa layers were carefully removed by sharp dissection, and special care was taken to avoid any damage to the underlying muscle layer.…”

Section: Gastrointestinal Smooth Muscle Mechanical Responsementioning

confidence: 99%

Caffeine impairs gastrointestinal function in newborn rats

2015

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Background: Feeding intolerance is commonly documented in premature infants. Caffeine is routinely utilized for apnea of prematurity treatment and known to reduce the lower esophageal sphincter (LES) muscle tone, but the caffeine effect on the newborn gastrointestinal function is unknown. We hypothesized that caffeine impairs esophageal and gastrointestinal motor function. As such, we investigated the drug effect on the tissue's mechanical properties and the newborn rat's in vivo gastric emptying rate. Methods: The effects of caffeine on LES, gastric fundal and antrum, as well as ileal and colonic muscle force potential and relaxation response, were measured in newborn and adult rats. The caffeine-induced (10 mg/kg i.p.) newborn gastric emptying rate changes were evaluated following 3 h of fasting. results: Caffeine relaxed the precontracted LES and fundal muscle (P < 0.01), reduced the gastric and intestinal muscle contraction (P < 0.01), and delayed the pups' gastric emptying time (P < 0.01). The caffeine-induced muscle relaxant effect was independent of age and mediated via ryanodine receptors. conclusion: Caffeine administration to newborn rats at a dose comparable to the one therapeutically used for preterm neonates impairs LES and gastrointestinal motor function. Further clinical investigation on the possible contribution of caffeine to neonatal feeding intolerance is warranted.

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In vitroeffect of pantoprazole on lower esophageal sphincter tone in rats

Cited by 6 publications

References 35 publications

Pantoprazole decreases gastroesophageal muscle tone in newborn rats via rho-kinase inhibition

Pantoprazole decreases gastroesophageal muscle tone in newborn rats via rho-kinase inhibition

Combined Therapy Effect of D-002 and Omeprazole on Chronic Esophagitis Induced by Duodenal Reflux in Rats

Caffeine impairs gastrointestinal function in newborn rats

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