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Nerve-Gut Research Laboratory, Level 1 Hanson Centre, Adelaide SA 5000, Australia
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.
gastric mechanoreceptors; vagus nerve
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