VITAMIN-K COUNTERACTS THE EFFECT OF WARFARIN IN LIVER BUT NOT IN BONE
VITAMIN-K COUNTERACTS THE EFFECT OF WARFARIN IN LIVER BUT NOT IN BONE
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DOI：
10.1016/0049-3848(87)90212-x
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发表时间：
1987-04-01
影响因子：
7.5
通讯作者：
KANEDA, Y
中科院分区：
文献类型：
--
作者：
PRICE, PA;KANEDA, Y
用高剂量的维生素K治疗完全抑制了华法林对血液凝固的作用但基本上没有能力抵消华法林对γ的作用。-骨玻璃蛋白羧化（骨钙素）。如果大鼠在服用华法林之前和同时服用适当剂量的维生素K，那么每100 g体重每天服用7.7 mg华法林对凝血次数没有影响。这个华法林的剂量大约是50亩的150倍。这导致没有服用维生素k的大鼠凝血时间翻倍。与之形成鲜明对比的是，华法林的剂量需要降低。- BGP羧化状态降至正常的一半，30 .mu。每100克体重g，基本上不受维生素K处理的影响。这些结果表明，合成凝血因子的肝细胞和合成BGP的成骨细胞对维生素K的代谢存在重大差异。这种差异的实际结果是，现在有可能在成骨细胞以及其他具有相同维生素K代谢的细胞中拮抗维生素K的作用，而不影响血液凝固时间。
Treatment with high dosages of Vitamin K completely inhibited the effect of Warfarin on blood coagulation but had essentially no ability to counteract the effect of Warfarin on the .gamma.-carboxylation of bone Gla protein (BGP; osteocalcin). Provided that rats received the appropriate dosage of Vitamin K prior to and concurrent with the administration of Warfarin, daily dosages as high as 7.7 mg Warfarin per 100 g body weight had no effect on blood coagulation times. This Warfarin dosage is approximately 150 times higher than the 50 .mu.g per 100 g body weight which caused coagulation times to double in rats which did not receive Vitamin K. In dramatic contrast, the dosage of Warfarin required to reduce the .gamma.-carboxylation status of BGP to one-half normal, 30 .mu.g per 100 g body weight, was essentially unaffected by Vitamin K treatment. These results indicate the existence of a major difference between the metabolism of Vitamin K by the hepatocytes which synthesize coagulation factors and the osteoblasts which synthesize BGP. The practical consequence of this difference is that it is now possible to antagonize the action of Vitamin K in osteoblasts, as well as in other cells which have the same Vitamin K metabolism, without affecting blood coagulation times.