Details

Autor(en) / Beteiligte

• Toyohira, Yumiko
• Yanagihara, Nobuyuki
• Minami, Kouichiro
• Ueno, Susumu
• Uezono, Yasuhito
• Tachikawa, Eiichi
• Kondo, Yukiko
• Kashimoto, Takeshi
• Izumi, Futoshi

Titel

Down‐Regulation of the Noradrenaline Transporter by Interferon‐α in Cultured Bovine Adrenal Medullary Cells

Ist Teil von

• Journal of neurochemistry, 1998-04, Vol.70 (4), p.1441-1447

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• : The aim of this study was to investigate the effect of long‐term treatment with interferon (IFN)‐α on the noradrenaline transporter of bovine adrenal medullary cells. Treatment of cultured adrenal medullary cells with IFN‐α caused a decrease in uptake of [3H]noradrenaline by the cells in time (4–48 h)‐ and concentration (300–1,000 U/ml)‐dependent manners. IFN‐β also inhibited [3H]noradrenaline uptake to a lesser extent than did IFN‐α, whereas IFN‐γ had little effect. An anti‐IFN‐α antibody reduced the effect of IFN‐α on [3H]noradrenaline uptake. Saturation analysis of [3H]noradrenaline uptake showed that the inhibitory effect of IFN‐α was due to a reduction in the maximal uptake velocity (Vmax) values without altering apparent Michaelis constant (Km) values. Incubation of cells with IFN‐α caused a translocation of protein kinase C from the soluble to the particulate fraction in the cells. The effect of IFN‐α on [3H]noradrenaline uptake was diminished in protein kinase C‐down‐regulated cells. Incubation of cells with IFN‐α for 48 h significantly reduced the specific binding of [3H]desipramine to crude plasma membranes isolated from cells. Scatchard analysis of [3H]desipramine binding revealed that IFN‐α decreased the maximal binding (Bmax) values without any change in the dissociation constant (KD) values. These findings suggest that IFN‐α suppresses the function of noradrenaline transporter by reducing the density of the transporter in cell membranes through, at least in part, a protein kinase C pathway.