- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
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.
- MeSH
- aferentní nervové dráhy účinky léků fyziologie MeSH
- baklofen aplikace a dávkování MeSH
- ezofágus účinky léků inervace fyziologie MeSH
- ganglion inferius účinky léků fyziologie MeSH
- morčata MeSH
- nervový útlum účinky léků fyziologie MeSH
- receptory GABA-A - agonisté aplikace a dávkování MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
