Identification of a novel regulatory mechanism for norepinephrine transporter activity by the IP₃ receptor

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• 作者：Taiju Amano ; Shunsuke Aoki ; Rieko Setsuie ; Mikako Sakurai ; Keiji Wada and Mami Noda
• 关键词：Norepinephrine ; Transporter ; Calcium ; Membrane traffic
• 刊名：European Journal of Pharmacology
• 出版年：2006
• 出版时间：24 April 2006
• 年：2006
• 卷：536
• 期：1-2
• 页码：62-68
• 全文大小：383 K

文摘

The norepinephrine transporter (NET) plays a crucial role in noradrenergic neurotransmission and is a target of many antidepressants and psychostimulants. Intracellular Ca²⁺ is reportedly involved in regulating NET activity, but the detailed mechanism is not clear. We employed a norepinephrine uptake assay using SH-SY5Y cells and found that the IP₃ receptor inhibitors, 2-aminoethoxydiphenyl borate and xestospongin C, reduced the NET V_max. These reductions were accompanied by the decreased cell surface expression of NET. Our findings suggest that intracellular Ca²⁺ mobilized by IP₃ receptor is required for the maintenance of NET activity. This adds another pathway involving Ca²⁺ for the regulation of NET to other known mechanisms providing intracellular Ca²⁺.