Effect of methylguanidine, guanidine and structurally related compounds on constitutive and inducible nitric oxide synthase activity

被引:13
|
作者
Sorrentino, R [1 ]
Sautebin, L [1 ]
Pinto, A [1 ]
机构
[1] UNIV SALERNO,DEPT PHARMACEUT SCI,I-84084 PENTA,SALERNO,ITALY
关键词
methylguanidine; guanidine; creatine; creatinine; nitric oxide synthase;
D O I
10.1016/S0024-3205(97)00673-5
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The inhibitory activity of methylguanidine, guanidine and their precursors, creatine and creatinine, on both the neuronal constitutive and lung inducible isoforms of nitric oxide synthase were examined in this study. Methylguanidine and guanidine (0.01-3 mM) significantly (P<0.01) inhibited in a concentration-dependent manner both isoforms of the enzyme. Furthermore analysis of the inhibition curves by ANOVA revealed that methylguanidine and guanidine act as non selective inhibitors of both nitric oxide synthases (P>0.4 for both methylguanidine and guanidine). In contrast, creatine and creatinine, although containing guanidine group, were totally ineffective on either enzyme even at concentration up to 3 mM. The results obtained for tested compounds also suggest a role for the lateral chain of guanidine group in the enzyme inhibition. The lack of selectivity of methylguanidine and guanidine in inhibiting both the nitric oxide synthase enzymes could account for some pathological manifestations like neurological disorders, host defense impairment and probably hypertension, that often occur in patients with uremia or chronic renal failure.
引用
收藏
页码:1283 / 1291
页数:9
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