Expression of GABAergic system in pulmonary neuroendocrine cells and airway epithelial cells in GAD67-GFP knock-in mice.
Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain, is also located in many peripheral nonneuronal tissues. The glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mouse is a useful model for studying the distribution of GABAergic cells in many tissues and organs. The lungs of these mice contain cells with an intense GFP signal exclusively in the airway epithelium. We aimed to characterize the GFP-positive cells and to clarify their relationship with the GABAergic system. We identified the GFP-positive cells as pulmonary neuroendocrine cells (PNECs) by immunohistochemistry for the protein gene product 9.5 and calcitonin gene-related peptide and by ultrastructural analysis. Immunohistochemistry for GADs and GABA revealed GAD65/67 and GABA in GFP-positive PNECs. Reverse transcription-polymerase chain reaction analyses revealed mRNAs encoding the GABA(B) receptor subunits necessary for the assembly of functional receptors, R1 and R2, in the lung. GABA(B) receptor subunit R1 and R2 proteins were expressed in many airway epithelial cells including alveolar epithelial cells other than GFP-positive PNECs. The present findings demonstrated that PNECs in the airway epithelium have a GABA production system and indicated that GABA plays functional roles in airway epithelial cells through GABA(B) receptors.
Yabumoto
Yasuaki
Y
Department of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Watanabe
Masahito
M
Ito
Yuko
Y
Maemura
Kentaro
K
Otsuki
Yoshinori
Y
Nakamura
Yumi
Y
Yanagawa
Yuchio
Y
Obata
Kunihiko
K
Watanabe
Katsuya
K
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009490:Neurosecretory Systems / Q000166:cytology* / Q000378:metabolism*; D021122:Protein Subunits; D018080:Receptors, GABA-B / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D017931:DNA Primers; D021122:Protein Subunits; D018080:Receptors, GABA-B; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2