Triggering of transient LES relaxations in ferrets: role of sympathetic pathways and effects of baclofen.
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.
Staunton
E
E
Nerve-Gut Research Laboratory, Department of Gastrointestinal Medicine, Royal Adelaide Hospital, South Australia, Australia.
Smid
S D
SD
Dent
J
J
Blackshaw
L A
LA
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*
D009125:Muscle Relaxants, Central; D018080:Receptors, GABA-B; D001418:Baclofen; D005947:Glucose; D002211:Capsaicin