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Enhancing and inhibitory effects of nitric oxide on superoxide anion generation in human polymorphonuclear leukocytes
Author(s) -
Morikawa Masako,
Inoue Michiko,
Tokumaru Satoko,
Kogo Hiroshi
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15040.x
Subject(s) - sodium nitroprusside , superoxide , nitric oxide , chemistry , intracellular , medicine , biochemistry , biophysics , endocrinology , biology , organic chemistry , enzyme
1 The effects of sodium nitroprusside (SNP, a nitric oxide donor) and authentic nitric oxide (NO) on superoxide anion (O 2 − ) generation were investigated in human polymorphonuclear leukocytes (PMNs). 2 Neither SNP (10 nM to 10 4μ m ) nor NO (40 nM to 40 μ m ) alone induced O 2 − generation or change of intracellular Ca 2+ concentration ([Ca 2+ ] i ) in human PMNs. 3 Pretreatment with SNP or NO at the concentrations used (SNP, 10 nM to 10 μm: NO, 40 nM to 40 μ m ) showed a biphasic concentration‐dependent effect on O 2 − 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 O 2 − generation and [Ca 2+ ] i elevation. On the other hand, high concentrations of SNP (10 μm) and NO (40 μ m ) alone elevated cyclic GMP levels and inhibited FMLP‐induced O 2 − generation and [Ca 2+ ]i elevation. 48 ‐Bromo‐cyclic GMP (8‐Br‐cyclic GMP) at concentrations ranging from 1 μ m to 1 mM did not induce O 2 − generation on its own and had little effect on FMLP‐induced O 2 − generation and [Ca 2+ ] i elevation. 5 Addition of a high concentration of NO (40 μ m ) decreased authentic O 2 − 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 O 2 − formation by pyrogallol. 6 In this study, we have shown that SNP and NO have dual effects (enhancement and inhibition) on O 2 − 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 O 2 − ‐scavenging effect and activation of the guanylate cyclase‐cyclic GMP pathway.