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Expression of GABAergic system in pulmonary neuroendocrine cells and airway epithelial cells in GAD67-GFP knock-in mice

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Abstract

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain, is also located in many peripheral nonneuronal tissues. The glutamate decarboxylase 67-green fl uorescent 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 GFPpositive 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 GABAB receptor subunits necessary for the assembly of functional receptors, R1 and R2, in the lung. GABAB 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 GABAB receptors.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, 569-8686, Japan

    Yasuaki Yabumoto, Masahito Watanabe, Yuko Ito, Kentaro Maemura & Yoshinori Otsuki

  2. Laboratory of Applied Microbiology and Biochemistry, Nara Women’s University, Nara, Japan

    Yumi Nakamura

  3. Department of Genetic and Behavioural Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Yuchio Yanagawa

  4. Neuronal Network Mechanisms Research Group, RIKEN Brain Science Institute, Saitama, Japan

    Kunihiko Obata

  5. Department of Hematology, Kinki University School of Medicine, Sayama, Osaka, Japan

    Katsuya Watanabe

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  1. Yasuaki Yabumoto
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  2. Masahito Watanabe
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  3. Yuko Ito
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  4. Kentaro Maemura
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  5. Yoshinori Otsuki
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  9. Katsuya Watanabe
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Correspondence to Masahito Watanabe.

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Yabumoto, Y., Watanabe, M., Ito, Y. et al. Expression of GABAergic system in pulmonary neuroendocrine cells and airway epithelial cells in GAD67-GFP knock-in mice. Med Mol Morphol 41, 20–27 (2008). https://doi.org/10.1007/s00795-007-0391-6

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  • DOI: https://doi.org/10.1007/s00795-007-0391-6

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