期刊论文详细信息
Journal of Pharmacological Sciences
Characterization of Noradrenaline-Induced Increases in Intracellular Ca2+ Levels in Chinese Hamster Ovary Cells Stably Expressing Human α1A-Adrenoceptor
Tadashi Nishiya1  Yumie Miyake1  Emi Kajita1  Atsushi Jinno1  Takahiro Horinouchi1  Arata Nishimoto1  Shoko Yorozu1  Soichi Miwa1 
[1] Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan
关键词: α1A-adrenoceptor;    store-operated channel;    nonselective cation channel;    Na+/Ca2+ exchanger;    intracellular free Ca2+ concentration;   
DOI  :  10.1254/jphs.FP0070891
学科分类:药学
来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society
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【 摘 要 】

References(38)Cited-By(3)The mechanism for noradrenaline (NA)-induced increases in intracellular Ca2+ concentration ([Ca2+]i) and physiological significance of Na+ influx through receptor-operated channels (ROCs) and store-operated channels (SOCs) were studied in Chinese hamster ovary (CHO) cells stably expressing human α1A-adrenoceptor (α1A-AR). [Ca2+]i was measured using the Ca2+ indicator fura-2. NA (1 μM) elicited transient and subsequent sustained [Ca2+]i increases, which were inhibited by YM-254890 (Gαq/11 inhibitor), U-73122 (phospholipase C (PLC) inhibitor), and bisindolylmaleimide I (protein kinase C (PKC) inhibitor), suggesting their dependence on Gαq/11/PLC/PKC. Both phases were suppressed by extracellular Ca2+ removal, SK&F 96365 (inhibitor of SOC and nonselective cation channel type-2 (NSCC-2)), LOE 908 (inhibitor of NSCC-1 and NSCC-2), and La3+ (inhibitor of transient receptor potential canonical (TRPC) channel). Reduction of extracellular Na+ and pretreatment with KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, inhibited both phases of [Ca2+]i increases. These results suggest that 1) stimulation of α1A-AR with NA elicits the transient and sustained increases in [Ca2+]i mediated through NSCC-2 that belongs to a TRPC family; 2) Na+ influx through these channels drives NCX in the reverse mode, causing Ca2+ influx in exchange for Na+ efflux; and 3) the Gαq/11/PLC/PKC-dependent pathway plays an important role in the increases in [Ca2+]i.

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