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

• Published in: European journal of pharmacology Vol. 519; no. 1-2; pp. 154 - 157
• Main Authors: Jensen, Jörgen, Lehmann, Anders, Uvebrant, Anna, Carlsson, Anita, Jerndal, Gunilla, Nilsson, Karolina, Frisby, Claudine, Blackshaw, L. Ashley, Mattsson, Jan P.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05.09.2005; Elsevier
• Subjects: 2-methyl-6-(phenylethynyl)-pyridine; Animals; Binding Sites; Binding, Competitive; Biological and medical sciences; Dogs; Dose-Response Relationship, Drug; Esophageal Sphincter, Lower - drug effects; Esophageal Sphincter, Lower - physiology; Esophagus; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - metabolism; Excitatory Amino Acid Antagonists - pharmacology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gastroesophageal reflux; Gastroesophageal Reflux - physiopathology; Gastroesophageal Reflux - prevention & control; Glutamate; Injections, Intravenous; Lower esophageal sphincter; Male; Medical sciences; MPEP; Muscle Relaxation - drug effects; Other diseases. Semiology; Pharmacology. Drug treatments; Pyridines - administration & dosage; Pyridines - metabolism; Pyridines - pharmacology; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - metabolism; Tritium; Gastroesophageal reflux; 2-methyl-6-(phenylethynyl)-pyridine; MPEP; Glutamate; Lower esophageal sphincter; Fissipedia; Carnivora; mglu5 glutamate receptor; Digestive system; Esophageal sphincter; Esophageal disease; Pyridine derivatives; Vertebrata; Mammalia; Animal; Excitatory aminoacid; Neurotransmitter; Digestive diseases; Antagonist; Dog
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.07.007

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 μmol/kg i.v.) produced a dose-dependent inhibition of transient lower esophageal sphincter relaxations (59±11% inhibition at 8.7 μmol/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.