Transient lower oesophageal sphincter relaxations--a pharmacological target for gastro-oesophageal reflux disease?
The oesophago-gastric junction functions as an anti-reflux barrier preventing increased exposure of the oesophageal mucosa to gastric contents. Failure of this anti-reflux barrier results in gastro-oesophageal reflux disease, and may lead to complications such as oesophagitis, Barrett's oesophagus and eventually oesophageal carcinoma. Recent studies have suggested that transient lower oesophageal sphincter relaxation is the main mechanism underlying gastro-oesophageal reflux. It involves a prolonged relaxation of the lower oesophageal sphincter, mediated by a vago-vagal neural pathway, synapsing in the brainstem. Several drugs, such as atropine, baclofen and loxiglumide, have been shown to reduce the rate of transient lower oesophageal sphincter relaxations and concomitantly the number of reflux episodes. These findings illustrate that transient lower oesophageal sphincter relaxations may represent a potential new target for the pharmacological treatment of gastro-oesophageal reflux disease. It is possible that the reduction in the number of transient lower oesophageal sphincter relaxations may also contribute to the beneficial effect of fundoplication and new endoscopic anti-reflux procedures. It should be emphasized, however, that other factors, such as low lower oesophageal sphincter pressure, the presence of a hiatal hernia and impaired oesophageal peristalsis, are also of great importance. Therefore, whether the targeting of transient lower oesophageal sphincter relaxations is the 'golden bullet' in anti-reflux therapy remains to be proven, as evidence of an effective control of gastro-oesophageal reflux in reflux patients is still lacking.
Hirsch
D P
DP
Academic Medical Centre, Division of Gastroenterology and Hepatology, Amsterdam, The Netherlands.
Tytgat
G N J
GN
Boeckxstaens
G E E
GE
D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D016099:Endoscopy, Gastrointestinal; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D018662:Fundoplication; D018755:GABA Agonists / Q000494:pharmacology; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D010276:Parasympatholytics / Q000494:pharmacology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D018755:GABA Agonists; D006727:Hormone Antagonists; D010276:Parasympatholytics; C053737:loxiglumide; D001285:Atropine; D011377:Proglumide; D001418:Baclofen