VII. EFFECTS OF DEFICIENCY 431 



Woolley^"" remarks that the dicoumarol-vitamin K antagonism differs 

 in several respects from the characteristic analog competitions: vitamin K 

 counteracts dicoumarol over only a limited dosage range; within this range 

 the inhibition index is not constant; and most unusual is an index of less 

 than 1.0 (for example, in the rat 10 mg. of dicoumarol is inhibited by 25 

 mg. of vitamin K; that is, an index of 0.4). 



Regardless of the exact nature of the antagonism between vitamin K and 

 dicoumarol, the recent evidence of Jacques' group^"^ suggests that the hepatic 

 cell is involved. Dicoumarol labeled with carbon^^ in the methylene bridge 

 was administered intravenously to mice and rabbits; significant radio- 



OH OH OH 



COO-C^Hs 







(12) (13) 



OH 



(15) 



OH OH OH 



(16) (1") 



Fig. 6. 



activity was found only in the liver, gallbladder, feces, and urine (only 

 degradation products in the urine). Intravenous administration of vitamin 

 K expedited disappearance of radioactivity from the mouse liver. Measur- 

 ing plasma dicoumarol directly, Shapiro et al}^^ were unable to demonstrate 

 more rapid disappearance of dicoumarol from the blood when vitamin K was 

 administered. Dicoumarol or its active products are apparently excreted by 

 the kidneys, for nephrectomy or experimental nephritis prolongs the anti- 

 coagulant activity.^" The suggestion'"^ has been made that the action of 



i°o D. W. WooUey, Physiol. Revs. 27, 308 (1947); Advances in Enzymol. 6, 129 (1946). 

 101 C. C. Lee, L. W. Trevoy, J. W. T. Spinks, and L. B. Jaques, Proc. Soc. Exptl. Biol. 



Med. 74, 151 (1950); J. W. T. Spinks and L. B. Jaques, Nature 166, 184 (1950). 

 '02 S. Shapiro, M. Weiner, and G. Simson, New Emjl. J. Med. 243, 775 (1950). 

 "3 p. Gley and J. Delor, Bull. soc. chim. biol. 30, 891 (1948); J. Badiu, C. Mentzer, J. 



Moraux, and P. Meunier, Coynpt. rend. soc. biol. 144, 871 (1950). 



