Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:L-citrulline recycling by argininosuccinate synthetase and lyase in rat gastric fundus. 1244 81

Polyaspartoyl.l-arginine (PDR) is an inhibitor of platelet aggregation ex vivo but in vitro. This study attempts to elucidate the target cell of PDR action and its action mechanism. PDR (1.7-170 microg/ml) significantly inhibited platelet aggregation in vitro in the presence of rat aortic endothelial cells (RAEC), NO synthase inhibitor N-nitro-l-arginine methyl ester (l-NAME) inhibited this effect, but it was ineffective in the RAEC absence. Correspondingly, PDR increased NO level in the supernatants of the platelet reactants in RAEC presence, but failed to influence NO level in RAEC absence, and these effects of PDR were more potent than those of l-arginine. Furthermore, PDR markedly elevated the intracellular level of l-arginine, and it (17-170 microg/ml) also augmented l-citrulline level in RAEC, argininosuccinate lyase (ASL) inhibitor succinate enhanced its effect on l-citrulline but l-NAME weakened it. 170 microg/ml of PDR slightly increased the l-aspartate level in RAEC, and succinate enhanced this effect. However l-arginine, l-aspartate or the combination of l-arginine and l-aspartate failed to change levels of these amino acids. In addition, PDR (170 microg/ml) stimulated the expression of argininosuccinate synthetase (ASS) protein. In conclusion, the endothelial cell is direct target cell of PDR's action; PDR facilitates the entry of l-arginine by serving as a carrier of l-arginine into RAEC; it also supplies aspartic acid and stimulates ASS expression, and then enhances the intracellular citrulline-NO cycle, thus increases the availability of l-arginine and NO synthesis. Therefore the effect of PDR on platelet aggregation is primarily attributed to its stimulation of NO synthesis in endothelial cells; PDR may be a better cardiovascular protective agent than l-arginine.
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PMID:Polyaspartoyl.l-arginine inhibits platelet aggregation through stimulation of NO release from endothelial cells. 1845 31

Bj-PRO-7a and Bj-PRO-10c belong to a family of proline-rich oligopeptides (PROs) identified in Bothrops jararaca (Bj) crude venom. Previous studies have shown an antihypertensive effect evoked by theses peptides. However, the mechanisms underlying the direct effects on vessels and heart remain to be unraveled. Thus, we investigated the effect of the Bj-PRO-7a and Bj-PRO-10c in the aorta and coronary arteries and in cardiac contractility in normotensive (Wistar) and hypertensive (SHR) rats. Pre-constricted aortic rings were exposed to increasing concentrations of Bj-PROs in presence or absence of muscarinic type 1 receptor antagonist (Pirenzepine), nonselective muscarinic receptor antagonist (Atropine), nitric oxide synthase inhibitor (L-NAME), guanylyl cyclase inhibitor (ODQ), adenylyl cyclase inhibitor (MDL), or argininosuccinate synthetase inhibitor (MDLA). The effects of Bj-PROs in the cardiac contractility and coronary vasomotricity were evaluated using Langendorff perfused heart preparation. The rat hearts were perfused with Bj-PRO-7a or Bj-PRO-10c in absence or presence of L-NAME, ODQ or MDL. Both Bj-PROs induced endothelium-dependent vasorelaxation in aortic rings from Wistars and SHRs. These effects were inhibited by L-NAME, ODQ or MDL. Atropine and Pirenzepine blocked the vasorelaxant effect of Bj-PRO-7a in aorta from both strains. MDLA inhibited the Bj-PRO-10c-induced vasorelaxation in aortic rings from SHR, but not Wistar. The Bj-PRO-7a induced coronary vasodilation only in SHR. L-NAME, ODQ and MDL inhibited this effect. Bj-PRO-10c induced coronary vasodilatation in both strains, which was blocked by L-NAME, ODQ and MDL. Bj-PRO-7a decreased the dP/dt max in Wistar hearts and the dP/dt min in Wistar and SHR hearts. These effects were abolished by L-NAME. Bj-PRO-10c decreased dP/dt max and dP/dt min in hearts from normotensive and hypertensive animals, which were abolished in the presence of L-NAME, MDL and ODQ. In summary, the Bj-PROs induced endothelium-dependent vasorelaxation in rat thoracic aorta, coronary vasodilation and negative inotropic effects through mechanisms mediated by activation of nitric oxide pathway.
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PMID:BJ-PRO-7A and BJ-PRO-10C induce vasodilatation and inotropic effects in normotensive and hypertensive rats: Role of nitric oxide and muscarinic receptors. 3035 32

Hematological and solid cancers catabolize the semiessential amino acid arginine to drive cell proliferation. However, the resulting low arginine microenvironment also impairs chimeric antigen receptor T cells (CAR-T) cell proliferation, limiting their efficacy in clinical trials against hematological and solid malignancies. T cells are susceptible to the low arginine microenvironment because of the low expression of the arginine resynthesis enzymes argininosuccinate synthase (ASS) and ornithine transcarbamylase (OTC). We demonstrate that T cells can be reengineered to express functional ASS or OTC enzymes, in concert with different chimeric antigen receptors. Enzyme modifications increase CAR-T cell proliferation, with no loss of CAR cytotoxicity or increased exhaustion. In vivo, enzyme-modified CAR-T cells lead to enhanced clearance of leukemia or solid tumor burden, providing the first metabolic modification to enhance CAR-T cell therapies.
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PMID:Metabolic engineering against the arginine microenvironment enhances CAR-T cell proliferation and therapeutic activity. 3257 23