Document Detail

Enhancing and inhibitory effects of nitric oxide on superoxide anion generation in human polymorphonuclear leukocytes.
MedLine Citation:
PMID:  7582560     Owner:  NLM     Status:  MEDLINE    
1. The effects of sodium nitroprusside (SNP, a nitric oxide donor) and authentic nitric oxide (NO) on superoxide anion (O2-) generation were investigated in human polymorphonuclear leukocytes (PMNs). 2. Neither SNP (10 nM to 10 microM) nor NO (40 nM to 40 microM) alone induced O2- generation or change of intracellular Ca2+ concentration ([Ca2+]i) in human PMNs. 3. Pretreatment with SNP or NO at the concentrations used (SNP, 10 nM to 10 microM: NO, 40 nM to 40 microM) showed a biphasic concentration-dependent effect on O2- generation induced by f-methionyl-leucyl-phenylalanine (FMLP). Low concentrations of SNP (10 nM to 100 nM) and NO (400 nM) did not affect either basal cyclic GMP levels or cyclic GMP levels stimulated by FMLP, but enhanced FMLP-induced O2- generation and [Ca2+]i elevation. On the other hand, high concentrations of SNP (10 microM) and NO (40 microM) alone elevated cyclic GMP levels and inhibited FMLP-induced O2- generation and [Ca2+]i elevation. 4. 8-Bromo-cyclic GMP (8-Br-cyclic GMP) at concentrations ranging from 1 microM to 1 mM did not induce O2- generation on its own and had little effect on FMLP-induced O2- generation and [Ca2+]i elevation. 5. Addition of a high concentration of NO (40 microM) decreased authentic O2- formation by pyrogallol in a cell-free system, but a low concentration of NO (400 nM) had no effect on this. On the other hand, addition of SNP in the concentration-ranges used had no effect on authentic O2- formation by pyrogallol. 6. In this study, we have shown that SNP and NO have dual effects (enhancement and inhibition) on 02- generation induced by FMLP in human peripheral PMNs. The results suggest that the enhancement observed with SNP and NO at low concentrations is not mediated by activation of the guanylate cyclase-cyclic GMP pathway. The suppressive effect of SNP and NO at higher concentrations is mediated by the NO-induced O2--scavenging effect and activation of the guanylate cyclase-cyclic GMP pathway.
M Morikawa; M Inoue; S Tokumaru; H Kogo
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  115     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-12-01     Completed Date:  1995-12-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1302-6     Citation Subset:  IM    
Department of Pharmacology, Tokyo College of Pharmacy, Hachioji, Japan.
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MeSH Terms
Calcium / metabolism
Cyclic GMP / analogs & derivatives,  pharmacology
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
Neutrophils / drug effects*,  metabolism
Nitric Oxide / physiology*
Nitroprusside / pharmacology
Pyrogallol / pharmacology
Superoxides / metabolism*
Reg. No./Substance:
10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 15078-28-1/Nitroprusside; 31356-94-2/8-bromocyclic GMP; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; 7440-70-2/Calcium; 7665-99-8/Cyclic GMP; 87-66-1/Pyrogallol

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