title: L-citrulline recycling by argininosuccinate synthetase and lyase in rat gastric fundus.
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.
authors.affiliation: Heymans Institute of Pharmacology, Ghent University, De Pintelaan 185, B-9000 Gent, Belgium.
authors.forename: Lieve A
authors.initials: LA
authors.lastname: Van Geldre
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
authors.forename: Romain A
authors.initials: RA
authors.lastname: Lefebvre
mesh_terms: D000818:Animals; D001119:Arginase / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D001123:Argininosuccinate Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001124:Argininosuccinate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001125:Argininosuccinic Acid / Q000494:pharmacology; D001224:Aspartic Acid / Q000494:pharmacology; D002956:Citrulline / Q000378:metabolism* / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005748:Gastric Fundus / Q000201:enzymology / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D013869:Thiolester Hydrolases / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
chemical_list: D004791:Enzyme Inhibitors; D005973:Glutamine; D001125:Argininosuccinic Acid; D002956:Citrulline; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D001120:Arginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D001119:Arginase; D001123:Argininosuccinate Lyase; D001124:Argininosuccinate Synthase; D019331:NG-Nitroarginine Methyl Ester