title: Effect of amiloride on experimental acid-induced heartburn in non-erosive reflux disease.
abstract: BACKGROUND
  Acid-sensing ion channels (ASICs) are esophageal nociceptors that are candidates to mediate heartburn in non-erosive reflux disease (NERD). Amiloride, a diuretic, is known to inhibit ASICs. For this reason, we sought a role for ASICs in mediating heartburn by determining whether amiloride could block heartburn in NERD induced by esophageal acid perfusion.
  
  
  METHODS
  In a randomized double-blind crossover study, we perfused the esophagus with amiloride or (saline) placebo prior to eliciting acid-induced heartburn in patients with a history of proton pump inhibitor-responsive NERD. Those with NERD and positive modified Bernstein test were randomized to perfusion with amiloride, 1 mmol/l, or placebo for 5 min, followed by repeat acid-perfusion. Heartburn severity and time to onset was measured and the process repeated following crossover to the alternative agent.
  
  
  RESULTS
  14 subjects completed the study. Amiloride did not reduce the frequency (100 vs. 100 %) or severity of acid-induced heartburn (Mean 2.50 ± SEM 0.33 vs. 2.64 ± 0.45), respectively. There was a trend towards longer time to onset of heartburn for amiloride versus placebo (Mean 2.93 ± SEM 0.3 vs. 2.36 ± 0.29 min, respectively), though these differences did not reach statistical significance (p > 0.05).
  
  
  CONCLUSIONS
  Amiloride had no significant effect on acid-induced heartburn frequency or severity in NERD, although there was a trend towards prolonged time to onset of symptoms.
authors: Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA. wbulsiew@med.unc.edu
authors: William J
authors: WJ
authors: Bulsiewicz
authors: Nicholas J
authors: NJ
authors: Shaheen
authors: Mark B
authors: MB
authors: Hansen
authors: Amy
authors: A
authors: Pruitt
authors: Roy C
authors: RC
authors: Orlando
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000627:therapeutic use*; D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000584:Amiloride / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications*; D006356:Heartburn / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D006851:Hydrochloric Acid / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D000584:Amiloride; D006851:Hydrochloric Acid
references: Gastroenterology. 2005 Mar;128(3):771-8
references: 15765412
references: Gut. 2005 Oct;54(10):1408-15
references: 15987792
references: Gastroenterology. 1996 Nov;111(5):1200-5
references: 8898633
references: Neuroscience. 2006 May 12;139(2):699-709
references: 16515841
references: Am J Gastroenterol. 2004 Jan;99(1):13-22
references: 14687135
references: Gut. 2008 Dec;57(12):1654-64
references: 18682519
references: Eur J Gastroenterol Hepatol. 2004 Sep;16(9):897-902
references: 15316415
references: Am J Gastroenterol. 2005 Mar;100(3):537-42
references: 15743348
references: Am J Physiol Gastrointest Liver Physiol. 2004 Jan;286(1):G174-81
references: 14512287
references: Am J Physiol Cell Physiol. 2004 Aug;287(2):C395-402
references: 15197006
references: Neurogastroenterol Motil. 2009 Oct;21(10):1032-e82
references: 19566590
references: J Neurosci. 2004 Dec 1;24(48):10974-9
references: 15574747
references: Eur J Gastroenterol Hepatol. 2006 Mar;18(3):263-70
references: 16462539
references: J Clin Invest. 2002 Oct;110(8):1185-90
references: 12393854
references: Aliment Pharmacol Ther. 2011 May;33(10):1113-22
references: 21410733