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

Abstract:

: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.

journal_name

Life Sci

journal_title

Life sciences

authors

Sorrentino R,Sautebin L,Pinto A

doi

10.1016/s0024-3205(97)00673-5

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

1283-91

issue

13

eissn

0024-3205

issn

1879-0631

pii

S0024320597006735

journal_volume

61

pub_type

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