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-fibres 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-fibres in baseline and/or in sensitized state induced by inflammatory mediators. Ex vivo extracellular recordings were made from the esophageal nodose C-fibres in the isolated vagally-innervated guinea pig esophagus. We found that the selective GABAB agonist baclofen (100-300µM) did not inhibit activation of esophageal nodose C-fibres evoked by esophageal distention (10-60mmHg). The mechanical response of esophageal nodose C-fibres 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 C-fibres induced by histamine (100µM) or the selective adenosine A2A receptor agonist CGS21680 (3nM). Our data suggest that the direct mechanical inhibition of nodose C-fibres in the esophagus is unlikely to contribute to beneficial effects of GABAB agonists in patients with esophageal diseases. Key words: Esophagus ● Vagal nodose C-fibres ● Extracellular nerve recording ● GABAB agonist
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