Functional expression of GABAB receptors in airway epithelium

Kentaro Mizuta, Yoko Osawa, Fumiko Mizuta, Dingbang Xu, Charles W. Emala

研究成果: Article査読

34 被引用数 (Scopus)


γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABAA) and metabotropic (GABAB) receptors. The GABAB receptor is a dimer composed of R1 and R2 components and classically couples to the heterotrimeric Gi protein. In addition to their location on neurons, GABA and functional GABAB receptors have been detected in peripheral tissue such as airway smooth muscle. We questioned whether airway epithelium expresses receptors that could respond to GABA. We detected the mRNA encoding multiple-splice variants of the GABABR1 and GABABR2 in total RNA isolated from native human and guinea pig airway epithelium and humanairway epithelial cell lines (BEAS-2Band H441). Immunoblots identified the GABABR1 and GABABR2 proteins in both guinea pig airway epithelium and BEAS-2B cells. The expression of GABABR1 protein was immunohistochemically localized to basal mucin-secreting and ciliated columnar epithelial cells in guinea pig trachea. Baclofen inhibited adenylyl cyclase activity, induced ERK phosphorylation and cross-regulated phospholipase C, leading to increased inositol phosphates in BEAS-2B cells in a pertussis toxin-sensitive manner, implicating Gi protein coupling. Thus, these receptors couple to Gi and cross-regulate the phospholipase C/inositol phosphate pathway. The second messengers of these pathways, cyclic AMP and calcium, play pivotal roles in airway epithelial cell primary functions of mucus clearance. Furthermore, the enzyme that synthesizes GABA, glutamic acid decarboxylase (GAD65/67), was also localized to airway epithelium. GABA may modulate an uncharacterized signaling cascade via GABAB receptors coupled to Gi protein in airway epithelium.

ジャーナルAmerican journal of respiratory cell and molecular biology
出版ステータスPublished - 2008 9月 1

ASJC Scopus subject areas

  • 分子生物学
  • 呼吸器内科
  • 臨床生化学
  • 細胞生物学


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