Evaluation of the effect of GABAB agonists on the vagal nodose C-fibers in the esophagus

M. Brozmanová, L. Mazúrová, M. Tatár, M. Kollárik

Research output: Contribution to journalArticle

Abstract

Clinical studies showed that GABAB 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 GABAB 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 GABAB 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 GABAB agonist baclofen (100- 300 μM) 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 H1 receptor and the stimulation the adenosine A2A receptor. Baclofen failed to inhibit mechanical sensitization of esophageal nodose Cfibers induced by histamine (100 μM) or the selective adenosine A2A 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 GABAB agonists in patients with esophageal diseases.

Original languageEnglish (US)
Pages (from-to)285-295
Number of pages11
JournalPhysiological research / Academia Scientiarum Bohemoslovaca
Volume62
Issue number3
StatePublished - 2013

Keywords

  • Baclofen
  • Esophagus
  • Extracellular nerve recording
  • GABA agonists
  • Vagal nodose C-fibers

ASJC Scopus subject areas

  • Physiology

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