Article: Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle.
Nitric oxide : biology and chemistry
2007 Volume 17, Issue 3-4, Page(s) 115–121
Abstract: Nitric oxide (NO) is an important vasorelaxant produced along with L-citrulline from L-arginine in a reaction catalyzed by endothelial nitric oxide synthase (eNOS). Previous studies suggested that the recycling of L-citrulline to L-arginine is essential ... ...
Abstract | Nitric oxide (NO) is an important vasorelaxant produced along with L-citrulline from L-arginine in a reaction catalyzed by endothelial nitric oxide synthase (eNOS). Previous studies suggested that the recycling of L-citrulline to L-arginine is essential for NO production in endothelial cells. However, there is no direct evidence demonstrating the degree to which the recycling of L-citrulline to L-arginine is coupled to NO production. We hypothesized that the amount of NO formed would be significantly higher than the amount of L-citrulline formed due to the efficiency of L-citrulline recycling via the citrulline-NO cycle. To test this hypothesis, endothelial cells were incubated with [14C]-L-arginine and stimulated by various agents to produce NO. The extent of NO and [14C]-L-citrulline formation were simultaneously determined. NO production exceeded apparent L-citrulline formation of the order of 8 to 1, under both basal and stimulated conditions. As further support, alpha-methyl-DL-aspartate, an inhibitor of argininosuccinate synthase (AS), a component of the citrulline-NO cycle, inhibited NO production in a dose-dependent manner. The results of this study provide evidence for the essential and efficient coupling of L-citrulline recycling, via the citrulline-NO cycle, to endothelial NO production. |
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MeSH term(s) | Animals ; Aorta/cytology ; Arginine/metabolism ; Argininosuccinate Synthase/antagonists & inhibitors ; Bradykinin/pharmacology ; Cattle ; Cell Survival/drug effects ; Cells, Cultured ; Citrulline/metabolism ; Dose-Response Relationship, Drug ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Enzyme Inhibitors/pharmacology ; Models, Biological ; N-Methylaspartate/analogs & derivatives ; N-Methylaspartate/pharmacology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Vanadates/pharmacology |
Chemical Substances | Enzyme Inhibitors ; Citrulline (29VT07BGDA) ; Nitric Oxide (31C4KY9ESH) ; Vanadates (3WHH0066W5) ; N-Methylaspartate (6384-92-5) ; 2-methylaspartic acid (866-73-9) ; Arginine (94ZLA3W45F) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Argininosuccinate Synthase (EC 6.3.4.5) ; Bradykinin (S8TIM42R2W) |
Language | English |
Publishing date | 2007-11 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 1362794-6 |
ISSN | 1089-8611 ; 1089-8603 |
ISSN (online) | 1089-8611 |
ISSN | 1089-8603 |
DOI | 10.1016/j.niox.2007.07.001 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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