کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9921223 1559207 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Homocysteine, a risk factor for atherosclerosis, biphasically changes the endothelial production of kynurenic acid
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Homocysteine, a risk factor for atherosclerosis, biphasically changes the endothelial production of kynurenic acid
چکیده انگلیسی
Increased serum level of homocysteine is an independent risk factor for vascular disease. The effect of dl-homocysteine on the endothelial production of kynurenic acid, an antagonist of α7-nicotinic and N-methyl-d-aspartate (NMDA) glutamate receptors, has been evaluated in vitro and in vivo. In rat aortic rings, dl-homocysteine at 40-100 μM enhanced, whereas at ≥ 400 μM decreased the synthesis of kynurenic acid. S-adenosylhomocysteine mimicked the biphasic action of dl-homocysteine. On the contrary, thiol-containing compounds, l-cysteine and l-methionine, were only inhibiting kynurenic acid production. l-kynurenine uptake blockers, l-phenylalanine and l-leucine, reversed the stimulatory effect of S-adenosylhomocysteine. l-glycine, co-agonist of NMDA receptor, and cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755), an antagonist of NMDA receptor, have not influenced kynurenic acid formation. In vivo, dl-homocysteine (1.3 mmol, i.p.) increased the level of kynurenic acid in rat serum from 23.7 ± 7.1 to 60.7 ± 14.2 (15 min, P < 0.01) and 55.7 ± 13.6 (60 min, P < 0.01) pmol/ml, respectively; the endothelial content of kynurenic acid was also increased (51.6 ± 5.8 vs. 73.2 ± 9.4 fmol/μg of protein; 15 min; P < 0.01). dl-homocysteine seems to modulate the production of kynurenic acid both directly and indirectly, possibly following the conversion to S-adenosylhomocysteine. The obtained data suggest a potential contribution of altered formation of kynurenic acid to the endothelial changes induced by hyperhomocysteinemia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 517, Issue 3, 11 July 2005, Pages 217-223
نویسندگان
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