title: Presence of GABA(B) receptors forming heterodimers with GABA(B1) and GABA(B2) subunits in human lower esophageal sphincter.
abstract: 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 findings 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.
authors.affiliation: Division of Surgery, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Torashima
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
authors.forename: Masato
authors.initials: M
authors.lastname: Kanaide
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ando
authors.forename: Akihito
authors.initials: A
authors.lastname: Enjoji
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Taniyama
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D049630:Esophageal Sphincter, Lower / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000096:biosynthesis; D009130:Muscle, Smooth / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000199:Actins; C546264:GABRB1 protein, human; C495710:GABRB2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B