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Expression of GABAA and GABAB receptors in rat growth plate chondrocytes: Activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells

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Abstract

Our previous study showed the local production of γ-aminobutyrate (GABA) in hypertrophic-zone chondrocytes of the rat tibial growth plate, an important long bone growth site. The aim of this study was to identify the presence of GABA receptors in growth plate chondrocytes by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Chondrocytes expressed both GABAA and GABAB receptor subunit mRNAs as well as the corresponding proteins necessary for the assembly of functional receptors. The GABAA receptor subunits detected included α1–α4, α6, β1–β3, and δ, and both R1 and R2 subunits of GABAB receptors were detected. All receptor subunits were expressed in chondrocytes of the proliferative and hypertrophic zones. These results suggest that GABA is an autocrine/paracrine factor that regulates the physiological state of the growth plate. Subsequent studies with the mouse chondrogenic cell line ATDC5 showed the presence of mRNAs and the corresponding proteins for GABAA receptor α1, β2, and β3 subunits and GABAB receptor R1 and R2 subunits. GABA, muscimol (a GABAA receptor agonist), and baclofen (a GABAB receptor agonist) increased 5-bromodeoxyuridine (BrdU) incorporation into ATDC5 cells. The effect of muscimol was blocked by bicuculline (a GABAA receptor antagonist), and the effect of baclofen was blocked by CGP 35348 (a GABAB receptor antagonist). These results suggest that GABA contributes to the ATDC5 cell proliferation via GABAA and GABAB receptors and these mechanisms may be involved in cartilaginous cell growth.

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Authors and Affiliations

  1. Department of Anatomy, Osaka Medical College, Takatsuki, Osaka, Japan

    Takumi Tamayama, Kentaro Maemura, Kiyoto Kanbara, Hana Hayasaki, Yasuaki Yabumoto, Masayoshi Yuasa & Masahito Watanabe

  2. Department of Anatomy, Osaka Medical College, Takatsuki, Osaka, 569-8686, Japan

    Masahito Watanabe

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  1. Takumi Tamayama
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  2. Kentaro Maemura
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  4. Hana Hayasaki
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  5. Yasuaki Yabumoto
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  6. Masayoshi Yuasa
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  7. Masahito Watanabe
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Correspondence to Masahito Watanabe.

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Tamayama, T., Maemura, K., Kanbara, K. et al. Expression of GABAA and GABAB receptors in rat growth plate chondrocytes: Activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells. Mol Cell Biochem 273, 117–126 (2005). https://doi.org/10.1007/s11010-005-8159-6

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  • DOI: https://doi.org/10.1007/s11010-005-8159-6

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