Abstract
The aim of this study was to investigate in rat gastric fundus whether L-citrulline, the co-product in the nitric oxide (NO) biosynthesis catalyzed by neuronal nitric oxide synthase (nNOS), can be converted back to the nNOS substrate L-arginine. Immunohistochemistry showed that argininosuccinate synthetase and argininosuccinate lyase, that mediate transformation of L-citrulline to L-arginine in the ureum cycle in hepatocytes, co-localize with nNOS. In longitudinal smooth muscle strips, L-arginine as well as L-citrulline (10(-3) M) was capable of completely respectively partially preventing the N(G)-nitro-L-arginine methyl ester (L-NAME) (3 x 10(-5) M)-induced inhibition of electrically induced nitrergic relaxations, whereas D-citrulline (10(-3) M) was not. The L-citrulline-mediated prevention of the L-NAME-induced inhibition was reduced by L-glutamine (3 x 10(-3) M), the putative L-citrulline uptake inhibitor, and by succinate, an argininosuccinate lyase inhibitor. The results demonstrate that the L-citrulline recycling mechanism is active in rat gastric fundus. Recycling of L-citrulline might play a role in providing sufficient amounts of nNOS substrate during long-lasting relaxations in gastric fundus after food intake.
Copyright 2002 Elsevier Science B.V.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arginase / pharmacology
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Arginine / metabolism
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Arginine / pharmacology
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Argininosuccinate Lyase / antagonists & inhibitors
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Argininosuccinate Lyase / metabolism*
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Argininosuccinate Synthase / antagonists & inhibitors
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Argininosuccinate Synthase / metabolism*
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Argininosuccinic Acid / pharmacology
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Aspartic Acid / pharmacology
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Citrulline / metabolism*
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Citrulline / pharmacology
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Dinoprost / pharmacology
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Gastric Fundus / enzymology
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Gastric Fundus / metabolism*
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Glutamic Acid / pharmacology
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Glutamine / pharmacology
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In Vitro Techniques
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Male
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Muscle Relaxation / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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N-Methylaspartate / pharmacology
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type I
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Rats
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Rats, Wistar
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Thiolester Hydrolases / metabolism
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Ubiquitin Thiolesterase
Substances
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Enzyme Inhibitors
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Glutamine
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Argininosuccinic Acid
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Citrulline
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Aspartic Acid
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Glutamic Acid
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N-Methylaspartate
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Arginine
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Dinoprost
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat
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Thiolester Hydrolases
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Ubiquitin Thiolesterase
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Arginase
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Argininosuccinate Lyase
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Argininosuccinate Synthase
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NG-Nitroarginine Methyl Ester