Horishita Takafumi, Minami Kouichiro, Yanagihara Nobuyuki, Shiraishi Munehiro, Okamoto Takashi, Shiga Yousuke, Ueno Susumu, Shigematsu Akio
Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Anesth Analg. 2002 Dec;95(6):1661-6, table of contents. doi: 10.1097/00000539-200212000-00034.
We studied the effects of alphaxalone, a neurosteroid anesthetic, on norepinephrine transporter (NET) function in cultured bovine adrenal medullary cells and the effect of a bolus injection of alphaxalone on blood pressure and serum norepinephrine (NE) levels in anesthetized rats. Alphaxalone (10-100 micro M) inhibited the desipramine-sensitive uptake of [(3)H]-NE by bovine adrenal medullary cells in a concentration-dependent manner. Eadie-Hofstee analysis of [(3)H]-NE uptake showed that alphaxalone increased the apparent Michaelis constant without altering the maximal velocity, indicating that inhibition occurred via competition for the NET. Alphaxalone inhibited the specific binding of [(3)H]-desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [(3)H]-desipramine binding revealed that alphaxalone increased the apparent dissociation constant for binding without altering maximal binding, indicating competitive inhibition. Bolus IV administration of alphaxalone had little effect on blood pressure but slightly, and significantly, increased the serum NE levels in anesthetized rats. These findings suggest that alphaxalone competitively inhibits NET function by interfering with both desipramine binding and NE recognition on the NET in adrenal medullary cells and probably in sympathetic neurons.
Alphaxalone inhibited the desipramine-sensitive uptake of [(3)H]-norepinephrine (NE) by interfering with desipramine binding in bovine adrenal medullary cells. A bolus IV administration of alphaxalone slightly and significantly increased the serum NE levels in anesthetized rats. These findings suggest that alphaxalone competitively inhibits NE transporter function probably in sympathetic neurons.
我们研究了神经甾体麻醉剂阿法沙龙对培养的牛肾上腺髓质细胞中去甲肾上腺素转运体（NET）功能的影响，以及一次性注射阿法沙龙对麻醉大鼠血压和血清去甲肾上腺素（NE）水平的影响。阿法沙龙（10 - 100微摩尔）以浓度依赖性方式抑制牛肾上腺髓质细胞对[³H]-NE的地昔帕明敏感摄取。对[³H]-NE摄取的伊迪-霍夫斯泰分析表明，阿法沙龙增加了表观米氏常数，而不改变最大速度，表明抑制是通过与NET竞争发生的。阿法沙龙抑制[³H]-地昔帕明与从牛肾上腺髓质分离的质膜的特异性结合。对[³H]-地昔帕明结合的斯卡查德分析表明，阿法沙龙增加了结合的表观解离常数，而不改变最大结合，表明竞争性抑制。一次性静脉注射阿法沙龙对血压影响不大，但略微且显著地增加了麻醉大鼠的血清NE水平。这些发现表明，阿法沙龙通过干扰肾上腺髓质细胞以及可能在交感神经元中NET上的地昔帕明结合和NE识别来竞争性抑制NET功能。
阿法沙龙通过干扰牛肾上腺髓质细胞中的地昔帕明结合来抑制[³H]-去甲肾上腺素（NE）的地昔帕明敏感摄取。一次性静脉注射阿法沙龙略微且显著地增加了麻醉大鼠的血清NE水平。这些发现表明，阿法沙龙可能在交感神经元中竞争性抑制NE转运体功能。
Zotero 插件