Transient lower esophageal sphincter relaxations in dogs are inhibited by a metabotropic glutamate receptor 5 antagonist

Transient lower esophageal sphincter relaxation is the major mechanism for gastroesophageal reflux. The present study was initiated to investigate the potential effect of the metabotropic glutamate 5 (mGlu5) receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), on transient lower esophageal sphincter relaxations in the conscious dog. MPEP (1.4-8.7 mu mol/kg i.v.) produced a dose-dependent inhibition of transient lower esophageal sphincter relaxations (59 +/- 11 % inhibition at 8.7 mu mol/kg). In addition, there was a reduction of the number of reflux. episodes and an increase in latency time to the occurrence of the first transient lower esophageal sphincter relaxation. No effect was seen on basal lower esophageal sphincter pressure or on swallowing. It is concluded that the mGlu5 receptor antagonist MPEP potently inhibits transient lower esophageal sphincter relaxations and that the mGlu5 receptor is a potential target for treatment of gastroesophageal reflux disease. (c) 2005 Elsevier B.V. All rights reserved.