Down-Regulation of the Noradrenaline Transporter by Interferon-α in Cultured Bovine Adrenal Medullary Cells |
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Authors: | Yumiko Toyohira,Nobuyuki Yanagihara,Kouichiro Minami,Susumu Ueno,Yasuhito Uezono,&dagger Eiichi Tachikawa,&dagger Yukiko Kondo,&dagger Takeshi Kashimoto, Futoshi Izumi |
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Affiliation: | Departments of Pharmacology and; Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu;and; Department of Pharmacology, School of Medicine, Iwate Medical University, Morioka, Japan |
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Abstract: | Abstract: 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 ( V max) values without altering apparent Michaelis constant ( K m) 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 ( B max) values without any change in the dissociation constant ( K D) 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. |
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Keywords: | Adrenal medullary cells [3H]Desipramine binding Interferon-α Noradrenaline transporter Noradrenaline uptake Protein kinase C |
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