[The arginine paradox].
L-Arginine has attracted major interest because it has been identified as the natural substrate of nitric oxide synthase and is now recognized as a major player in the regulation of biological function. The arginine paradox refers to the phenomenon that exogenous L-arginine causes NO-mediated biological effects despite the fact that nitric oxide synthases (NOS) are theoretically saturated with the substrate L-arginine. There have been several explanations for this phenomenon, although none of them can explain the arginine paradox fully: (1) L-arginine-induced insulin, which has vasodilatory actions. (2) Neither extracellular nor intracellular concentration determines the NOS activity but rather the L-arginine amount transported across the plasma membrane may do so. (3) Endogenous NOS inhibitors reduce the enzyme sensitivity to L-arginine. These inhibitors include, NG, NG-dimethyl-L-arginine, L-citrulline, argininosuccinic acid and agmatine. (4) Intracellular L-citrulline, an NOS product, is a potent inhibitor of NOS so that the cells may need extra L-arginine to compete with L-citrulline inhibition.
Nakaki
Toshio
T
Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. nakaki@med.teikyo-u.ac.jp
Hishikawa
Keiichi
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001120:Arginine; D019001:Nitric Oxide Synthase