GABA(B)R expressed on vagal afferent neurones inhibit gastric mechanosensitivity in ferret proximal stomach

GABA(B)-receptor (GABA(B)R) agonists reduce transient lower esophageal sphi ncter relaxation (TLESR) and reflux episodes through an action on vagal pat hways. In this study, we determined whether GABA(B)R 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 bef ore and after perfusion with the GABA(B)R-selective agonists baclofen and 3 -aminopropylphosphinic acid (3-APPiA). Retrograde labeling and immunohistoc hemistry were used to identify GABA(B)R located on vagal afferent neurones in the nodose ganglia. Vagal afferent fibers responded to isovolumetric gas tric distension with an increase in discharge. The GABA(B)-receptor agonist s baclofen (5 x 10(-5) M) and 3-APPiA (10(-6) to 10(-5) M) but not muscimol (GABA(A)-selective agonist: 1.3 x 10(-5) M) significantly decreased affere nt distension-response curves. The effect of baclofen (5 x 10(-5) M) was re versed by the GABA(B)-receptor antagonist CGP 62349 (10(-5) M). Over 93% of retrogradely labeled gastric vagal afferents in the nodose ganglia express ed immunoreactivity for the GABA(B)R. GABA(B)R expressed on vagal afferent fibers directly inhibit gastric mechanosensory activity. This is likely a c ontributing mechanism to the efficacy of GABA(B)-receptor agonists in reduc ing TLESR and reflux episodes in vivo.