Possible expression of a particular gamma-aminobutyric acid transporter isoform responsive to upregulation by hyperosmolarity in rat calvarial osteoblasts

Sayumi Fujimori, Eiichi Hinoi, Takeshi Takarada, Mika Iemata, Yoshifumi Takahata, Yukio Yoneda

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the brain, but widely distributed in different peripheral organs. We have previously shown the functional expression of GABAB receptors required for GABAergic signal input by cultured rat calvarial osteoblasts. This study focused on the possible functional expression of the machinery required for GABAergic signal termination such as GABA transporters. In rat calvarial osteoblasts cultured for 7 days, [3H]GABA accumulation was observed in a temperature-, sodium- and chloride-dependent manner, consisting of a single component with a Km value of 789.6 ± 9.0 μM and a Vmax value of 4.4 ± 0.1 nmol/min/mg protein, respectively. Both nipecotic and l-2,4-diaminobutyric acids significantly inhibited [3H]GABA accumulation in a concentration-dependent manner. Constitutive expression was seen with mRNA for the betaine/GABA transporter-1 (BGT-1) and taurine transporter (TauT), while hyperosmotic cultivation led to significant increases in both [3H]GABA accumulation and BGT-1 mRNA expression without affecting TauT mRNA expression. Highly immunoreactive cells were detected for the BGT-1 isoform at the surface of trabecular bone of neonatal rat tibias. Sustained exposure to GABA significantly inhibited alkaline phosphatase (ALP) activity, but not cellular viability, at concentrations above 0.1 mM in osteoblasts cultured for 3 to 28 days. Nipecotic acid not only decreased ALP activity alone, but also further decreased ALP activity in osteoblasts cultured in the presence of GABA. These results suggest that the BGT-1 isoform may be functionally expressed by rat calvarial osteoblasts to play a hitherto unidentified role in mechanisms underlying hyperosmotic regulation of osteoblastogenesis.

Original languageEnglish
Pages (from-to)24-32
Number of pages9
JournalEuropean Journal of Pharmacology
Volume550
Issue number1-3
DOIs
Publication statusPublished - Nov 21 2006
Externally publishedYes

Fingerprint

Osteoblasts
gamma-Aminobutyric Acid
Protein Isoforms
Up-Regulation
GABA Plasma Membrane Transport Proteins
Alkaline Phosphatase
Messenger RNA
Betaine
Tibia
Sodium Chloride
Neurotransmitter Agents
Temperature
Brain
betaine plasma membrane transport proteins
Proteins

Keywords

  • [H]GABA accumulation
  • Betaine/GABA transporter
  • GABA
  • Osteoblast

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Possible expression of a particular gamma-aminobutyric acid transporter isoform responsive to upregulation by hyperosmolarity in rat calvarial osteoblasts. / Fujimori, Sayumi; Hinoi, Eiichi; Takarada, Takeshi; Iemata, Mika; Takahata, Yoshifumi; Yoneda, Yukio.

In: European Journal of Pharmacology, Vol. 550, No. 1-3, 21.11.2006, p. 24-32.

Research output: Contribution to journalArticle

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