title: Evaluation of the effect of GABA(B) agonists on the vagal nodose C-fibers in the esophagus.
abstract: Clinical studies showed that GABA(B) receptor agonists improve symptoms in patients with gastroesophageal reflux disease. One proposed mechanism of this effect is direct inhibition of the gastroesophageal vagal tension mechanosensors by GABA(B) agonists leading to reduction of reflux. In addition to tension mechanosensors, the vagal nodose ganglion supplies the esophagus with nociceptive C-fibers that likely contribute to impairment of esophageal reflex regulation in diseases. We hypothesized that GABA(B) agonists inhibit mechanically-induced activation of vagal esophageal nodose C-fibers in baseline and/or in sensitized state induced by inflammatory mediators. Ex vivo extracellular recordings were made from the esophageal nodose C-fibers in the isolated vagally-innervated guinea pig esophagus. We found that the selective GABA(B) agonist baclofen (100-300 microM) did not inhibit activation of esophageal nodose C-fibers evoked by esophageal distention (10-60 mmHg). The mechanical response of esophageal nodose C-fibers can be sensitized by different pathways including the stimulation of the histamine H(1) receptor and the stimulation the adenosine A(2A) receptor. Baclofen failed to inhibit mechanical sensitization of esophageal nodose C-fibers induced by histamine (100 microM) or the selective adenosine A(2A) receptor agonist CGS21680 (3 nM). Our data suggest that the direct mechanical inhibition of nodose C-fibers in the esophagus is unlikely to contribute to beneficial effects of GABA(B) agonists in patients with esophageal diseases.
authors.affiliation: Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. brozmanova@jfmed.uniba.sk
authors.forename: M
authors.initials: M
authors.lastname: Brozmanová
authors.forename: L
authors.initials: L
authors.lastname: Mazúrová
authors.forename: M
authors.initials: M
authors.lastname: Tatár
authors.forename: M
authors.initials: M
authors.lastname: Kollárik
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage*; D006168:Guinea Pigs; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000187:drug effects / Q000502:physiology*
chemical_list: D058785:GABA-A Receptor Agonists; D001418:Baclofen