Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors

Clavé, Père; González, A.; Moreno, Araceli; López, Regina Gálvez; Farré, A.J.; Segura, Xavier Cussó i; D’Amato, Massimo; Azpiroz, Fernando; Lluı́s, Fèlix

doi:10.1016/s0016-5085(98)70139-8

Cited by 67 publications

(66 citation statements)

References 28 publications

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“…At present, there are only a few pharmacological agents (morphine, cholecystokinin, atropine, baclofen) available for the treatment of acid reflux (Boulant et al, 1997;Mittal et al, 1997;Penagini et al, 1997;Boeckxstaens et al, 1998;Clavé et al, 1998,), however it is very difficult to use most of these drugs because they need to be injected and /or they have side-effects. It is possible for only baclofen to be effective in the treatment of acid reflux and it has been reported that baclofen, a gamma-aminobutyric acid B agonist, has been successful in decreasing the rate of TLESRs, as well as decreasing the number of acid reflux episodes in healthy subjects and patients with GERD (Lidums et al, 2000;Zhang et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

Iwakiri

Kawami

Sano

et al. 2011

J. Smooth Muscle Res.

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Background: A study in Japan has found that nizatidine (NIZ) is more effective than other histamine H2 receptor agonists (H2RAs) in treating reflux esophagitis (RE), although the NIZ group included a greater number of patients with severe RE. As there was no difference in the level of acid suppression among H2RAs, it is possible that NIZ has other effects on esophageal acid exposure (EAE) besides acid suppression. In this study, the effect of NIZ on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux was evaluated in healthy subjects. Methods: In 10 healthy subjects, while in a sitting position, esophageal motility and a pH study were measured for 3 hours after a meal on 2 separate days at least 2 weeks apart. Participants received an oral dose of 150 mg of NIZ, 60 min before the meal on one day and a placebo on the other. Both studies were preceded by a week of treatment with either NIZ (150 mg, bid) or a placebo and the order of treatment was randomized. Results: Basal LES pressure in the NIZ group (14.1 mmHg, median) was significantly greater than that of the placebo group (8.5 mmHg). The rate of TLESRs in the NIZ group (22.0/3 h) for the postprandial 3-hour period was significantly less than that of the placebo group (16.5/3 h) and the rate of acid reflux during TLESRs (24.7%) and the EAE (0.2%) in the NIZ group for the postprandial 3-hour period was also significantly less than that of the placebo group (74.4% and 2.8%, respectively). Conclusion: NIZ significantly reduces acid reflux by inhibiting both the rate of TLESRs and acid reflux during TLESRs.

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Section: Discussionmentioning

confidence: 99%

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

Iwakiri

Kawami

Sano

et al. 2011

J. Smooth Muscle Res.

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“…64,69 The rate of TLOSRs induced by meals and gastric distension can be decreased with a selective CCK-A receptor antagonist. [69][70][71][72] However, the effects of CCK and CCK antagonists on the rate of acid reflux are only modest.…”

Section: Other Neurotransmitters and Agentsmentioning

confidence: 99%

Review article: the clinical relevance of transient lower oesophageal sphincter relaxations in gastro-oesophageal reflux disease

Kessing

Conchillo

Bredenoord

et al. 2011

Alimentary Pharmacology &Amp; Therapeutics

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“…CCK-1(A) CCK-8 π (Boulant et al 1994;Clave et al 1998) Devazepide ª (Boulant et al 1994) Loxiglumide ª (Boeckxstaens et al 1998;Boulant et al 1997;Zerbib et al 1998) GABA B Baclofen ª (Blackshaw et al 1999;Lehmann et al 1999;Lidums et al 2000;Zhang et al 2002) Muscarinic Atropine ª (Mittal et al 1997;Lidums et al 1998) Methylscopolamine 0 (Fang et al 1999) Hyocine butylbromide 0 (Lidums et al 1997)…”

Section: Receptorsmentioning

confidence: 99%

Pharmacological Targets in Gastro‐Oesophageal Reflux Disease

Piche¹,

Galmiche²

2005

Basic Clin Pharma Tox

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Although proton pump inhibitors have become the mainstay of treatment in gastro-oesophageal reflux disease (GORD), there are still unmet needs in the management of this very common disorder. For example, all current proton pump inhibitors have a relatively slow onset of action and their activity is limited mainly to the post-prandial period with far less effective inhibition of nocturnal acid secretion. In order to achieve more potent, rapid and sustained acid inhibition several compounds are currently under development, such as new proton pump inhibitors with a prolonged plasma halflife, potassium competitive ATPase blockers (PCABs), histamine H 3 agonists, and gastrin antagonists. Acid suppression does not, however, cure the disease and relapses are frequently observed after discontinuation of proton pump inhibitor therapy. Among the different abnormalities involved in the pathophysiology of this multifactorial disease, transient lower oesophageal sphincter relaxations represent the major mechanism responsible for episodes of reflux. Baclofen, the prototype GABA B receptor agonist, is one of the most potent inhibitors of transient lower oesophageal sphincter relaxations identified. To date the transfer of these relaxation-controlling pharmacological agents into clinical practice has however been hampered by the occurrence of unacceptable side effects. Beside ''anti-relaxation therapy'', the potential of novel prokinetics such as motilin agonists has been explored, especially since the motilin receptor has been cloned. Thus far the broad therapeutic value of prokinetics in GORD does, however, seem very limited in terms of efficacy with respect to oesophageal motility and acid exposure. Lastly, further research is necessary to better understand the complex mechanisms involved in oesophageal sensitivity and mucosal defence.Although the aetiology of gastro-oesophageal reflux disease (GORD) is not precisely understood, its pathogenesis is clearly multifactorial; thus, there are many different potential therapeutic targets for drug development. Dysfunction of the lower oesophageal sphincter, the resultant reflux of gastric (and at times duodenal) contents into the oesophagus and the subsequent harmful effects of acid and pepsin on the oesophageal mucosa have been best identified, though they are not the only pathophysiological factors in GORD. During recent decades the central role of acid in the pathophysiology of both GORD symptoms and reflux oesophagitis has largely been confirmed by the therapeutic revolution of proton pump inhibitors. In contrast, the pharmacological control of mechanisms that ultimately result in the occurrence of reflux episodes has been far less successful. Gastro-oesophageal junction incompetence can result from various motility disturbances which are frequently but not necessarily associated with anatomical abnormalities (hiatus hernia). Transient relaxations of the lower oesophageal sphincter are typically not induced by swallowing and represent the major mechanAuthor for corres...

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Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors

Cited by 67 publications

References 28 publications

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

Review article: the clinical relevance of transient lower oesophageal sphincter relaxations in gastro-oesophageal reflux disease

Pharmacological Targets in Gastro‐Oesophageal Reflux Disease

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