Presence of GABAB Receptors Forming Heterodimers With GABAB1 and GABAB2 Subunits in Human Lower Esophageal Sphincter

Yasuhiro Torashima, Yasuhito Uezono, Masato Kanaide, Yuko Ando, Akihito Enjoji, Takashi Kanematsu, Kohtaro Taniyama
2009 Journal of Pharmacological Sciences  
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
more » ... 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.
doi:10.1254/jphs.09062fp pmid:19893276 fatcat:xvhcabzwrrfvpg5krlkvh6b3li