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EFFECT OF XANTHINE DERIVATIVES ON CHEMOTACTIC POLYPEPTIDE‐INDUCED SUPEROXIDE AND ENZYME RELEASE FROM HUMAN POLYMORPHONUCLEAR LEUCOCYTES
Author(s) -
Hirano Tsunekazu,
Ando Morihide,
Suzuki Kenji,
Furui Hidehiko,
Miyamoto Kenichi,
Takagi Kenzo
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01744.x
Subject(s) - superoxide , xanthine , lysozyme , chemistry , xanthine oxidase , superoxide dismutase , biochemistry , enzyme
SUMMARY 1. We investigated the effects of new xanthine derivatives, 1‐methyl‐3‐propyl xanthine (MPX) and 1,3‐dipropyl xanthine (DPX), and several other xanthine derivatives on N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced superoxide and lysozyme release from human polymorphonuclear leucocytes (PMN). 2. MPX and DPX at low concentrations (10 −8 ‐10 −9 mol/L) inhibited superoxide release from PMN by a maximum of 31.2 ± 10.6% and 49.8 ± 10.4% (mean ± s.d.), respectively, and 10 −3 mol/L concentrations completely inhibited the release reactions (4.8 ± 1.2 and 7.6 ± 2.5% of control level). At 10 −5 mol/ L, however, the inhibition did not occur (99.9 ± 7.3 and 110.2 ± 15.8% of control level). When PMN was pre‐incubated with adenosine deaminase (ADA, 0.1 U/mL), superoxide release from PMN was inhibited in a dose‐dependent manner by MPX and DPX and the interruption of the inhibition at 10 −5 mol/L was not observed. 3. Lysozyme release from PMN was inhibited by MPX at low concentrations (10 −7 ‐10 −6 mol/L) and high concentrations (10 −3 mol/L). However 10 −4 mol/L of MPX facilitated the release (23.7 ± 27.0%). When pretreated with ADA (0.1 U/mL), MPX suppressed lysozyme release in a dose‐dependent manner and the facilitation of the release at 10 −4 mol/L was not observed. 4. When comparing effects of some other xanthine derivatives on superoxide release, the interruption of the inhibition of superoxide release at 10 −5 mol/L was commonly observed among xanthine derivatives with adenosine A 2 antagonism. 5. The results suggest that adenosine A 2 antagonism of xanthine derivatives may interfere with their anti‐inflammatory effects at therapeutic concentrations (10 −5 ‐10 −4 mol/L).