Baclofen, a GABA B -receptor (GABA B R) agonist has been proposed to be useful as therapeutic agent for the management of gastro-esophageal reflux disease, but whether the compound acts directly at the lower esophageal sphincter (LES) remains to be elucidated. We performed the present study to assess the presence of GABA B R in human LES. Western blot analysis showed that both proteins of GABA B1(a) /GABA B1(b) and GABA B2 subunits were present in the muscle layer of LES. Immunohistochemical

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... dings showed that both GABA B1 -and GABA B2 -subunit proteins were located on the neurons within the myenteric plexus, and furthermore, both proteins were observed in the same neurons. Reverse transcriptase-polymerase chain reaction analysis also revealed the presence of mRNAs for both subunits of GABA B R and also mRNAs for 6 isoforms of GABA B1 subunits, from GABA B1(a) to GABA B1(g) , except GABA B1(d) , in human LES. Thus, the functional GABA B R-forming heterodimers with subunits of GABA B1 and GABA B2 are located on the myenteric neurons in human LES, suggesting that GABA B R agonists and antagonists act at least, at the level of the peripheral nervous system.