Bile acids cause relaxation of the lower esophageal sphincter through G-protein-coupled bile acid receptors

ObjectivesBile acids inhibit contraction of the gallbladder and intestine through the G-protein-coupled bile acid receptor (GPBAR). Perfusion of the esophagus with bile and acid (HCl) decreases lower esophageal sphincter (LES) pressure. The effects of bile acids on LES motility are not clear. The purpose of the present study was to investigate the effects of bile acids on LES motility in vitro.Materials and MethodsWe measured the relaxation of muscle strips isolated from guinea pig and rat LES caused by bile acids or the selective GPBAR agonist RG-239. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine GPBAR expression in rat LES.ResultsIn carbachol-contracted guinea pig LES strips, lithocholic acid (LCA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), and cholic acid (CA) produced relaxation in a concentration-dependent manner. The relative potency was LCA ≥ DCA > CDCA > CA. RG-239 also induced concentration-dependent relaxation. This suggests that GPBAR mediates relaxation in guinea pig LES. DCA-induced LES relaxation was attenuated by the protein kinase A inhibitor KT 5720 but not by the protein kinase G inhibitor KT 5823 or the NO synthase inhibitor L-NNA. This suggests the involvement of cAMP. Separately, in endothelin-1-contracted rat LES strips, bile acids induced relaxation. The relative potency was LCA = DCA > CDCA > CA. RT-PCR revealed GPBAR expression in rat LES.ConclusionThese results demonstrate that bile acids cause relaxation of guinea pig and rat LES through GPBAR.