α-Guanidinoglutaric Acid, an Endogenous Convulsant, as a Novel Nitric Oxide Synthase Inhibitor |
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Authors: | Isao Yokoi Hideaki Kabuto Hitoshi Habu Akitane Mori |
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Institution: | Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Okayama, Japan |
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Abstract: | Abstract: The effects of α-guanidinoglutaric acid (GGA), the levels of which were increased in the cobalt-induced epileptic focus tissue in the cerebral cortex of cats, on brain nitric oxide synthase (NOS) activity were observed. GGA inhibited NOS activity in a linear mixed manner ( K i = 2.69 µ M ) and was as effective as N G-monomethyl- l -arginine (MeArg; K i = 3.51 µ M ), a well-known NOS inhibitor. Although MeArg was synthesized by substituting the guanidino nitrogen of l -arginine (Arg), GGA was a non-guanidino nitrogen-substituted guanidino compound. On the other hand, Arg, which is an endogenous NOS substrate, elevates the threshold of seizures induced by GGA. There is evidence that GGA is an endogenous, potent, and non-guanidino nitrogen-substituted NOS inhibitor and that suppression of nitric oxide biosynthesis may be involved in GGA-induced convulsions. Therefore, GGA may be a useful tool in elucidating the chemical nature of NOS and the physiological function of nitric oxide. |
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Keywords: | Nitric oxide Nitric oxide synthase Guanidino compound Guanidinoglutaric acid |
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