title: Triggering of transient LES relaxations in ferrets: role of sympathetic pathways and effects of baclofen.
abstract: Activation of gastric vagal mechanoreceptors by distention is thought to be the trigger for transient lower esophageal sphincter relaxations (TLESR), which lead to gastroesophageal reflux. The contribution of higher-threshold gastric splanchnic mechanoreceptors is uninvestigated. GABA(B) receptor agonists, including baclofen, potently reduce triggering of TLESR by low-level gastric distention. We aimed to determine first whether this effect of baclofen is maintained at high-level distention and second the role of splanchnic pathways in triggering TLESR. Micromanometric/pH studies in conscious ferrets showed that intragastric glucose infusion (25 ml) increased triggering of TLESR and reflux. Both were significantly reduced by baclofen (7 micromol/kg ip) (P < 0.05). When 40 ml of air was added to the glucose infusion, more TLESR occurred than with glucose alone (P < 0.01). These were also reduced by baclofen (P < 0.001). TLESR after glucose/air infusion were assessed before and after splanchnectomy (2-4, 9-11, and 23-25 days), which revealed no change. Baclofen inhibits TLESR after both low- and high-level gastric distention. Splanchnic pathways do not contribute to increased triggering of TLESR by high-level gastric distention.
authors.affiliation: Nerve-Gut Research Laboratory, Department of Gastrointestinal Medicine, Royal Adelaide Hospital, South Australia, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Staunton
authors.forename: S D
authors.initials: SD
authors.lastname: Smid
authors.forename: J
authors.initials: J
authors.lastname: Dent
authors.forename: L A
authors.initials: LA
authors.lastname: Blackshaw
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D004435:Eating; D004943:Esophagogastric Junction / Q000294:innervation* / Q000502:physiology*; D005260:Female; D005289:Ferrets; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology; D009121:Muscle Denervation; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000502:physiology; D011312:Pressure; D018080:Receptors, GABA-B / Q000502:physiology; D013153:Splanchnic Nerves / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*
chemical_list: D009125:Muscle Relaxants, Central; D018080:Receptors, GABA-B; D001418:Baclofen; D005947:Glucose; D002211:Capsaicin