GABABR expressed on vagal afferent neurones inhibit gastric mechanosensitivity in ferret proximal stomach

Scott D. Smid, Richard Young, Nicole Isaacs, L. Ashley Blackshaw

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Abstract

GABAB-receptor (GABABR)agonists reduce transient lower esophageal sphincter relaxation (TLESR) and reflux episodes through an action on vagal pathways. In this study, we determined whether GABABR are expressed on vagal afferent neurones and whether they modulate distension-evoked discharge of vagal afferents in the isolated stomach. Vagal mehanoreceptor activity was recorded following distensions of the isolated ferret proximal stomach before and after perfusion with the GABABR-selective agonists baclofen and 3-aminopropylphosphinic acid (3-APPiA). Retrograde labeling and immunohistochemistry were used to identify GABABR located on vagal afferent neurones in the nodose ganglia. Vagal afferent fibers responded to isovolumetric gastric distension with an increase in discharge. The GABAB-receptor agonists baclofen (5 × 10-5 M) and 3-APPiA (10-6 to 10-5 M) but not muscimol (GABAA-selective agonist: 1.3 × 10-5 M) significantly decreased afferent distension-response curves. The effect of baclofen (5 × 10-5 M) was reversed by the GABAB-receptor antagonist CGP 62349 (10-5 M). Over 93% of retrogradely labeled gastric vagal afferents in the nodose ganglia expressed immunoreactivity for the GABABR. GABABR expressed on vagal afferent fibers directly inhibit gastric mechanosensory activity. This is likely a contributing mechanism to the efficacy of GABAB-receptor agonists in reducing TLESR and reflux episodes in vivo.

Original languageEnglish
Pages (from-to)G1494-G1501
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number6 44-6
DOIs
Publication statusPublished or Issued - 1 Jan 2001

Keywords

  • Gastric mechanoreceptors
  • Vagus nerve

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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