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EFFECT OF XANTHINE DERIVATIVES ON CHEMOTACTIC POLYPEPTIDE-INDUCED SUPEROXIDE AND ENZYME RELEASE FROM HUMAN POLYMORPHONUCLEAR LEUCOCYTES
Authors:Tsunekazu Hirano  Morihide Ando  Kenji Suzuki  Hidehiko Furui  Kenichi Miyamoto  Kenzo Takagi
Affiliation:Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya;*Department of Internal Medicine, Ogaki Municipal Hospital, Gifu;Department of Respiratory Medicine, Higashinagoya Hospital, Nagoya;Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University, Kanazawa, Japan
Abstract: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 A2 antagonism. 5. The results suggest that adenosine A2 antagonism of xanthine derivatives may interfere with their anti-inflammatory effects at therapeutic concentrations (10?5-10?4 mol/L).
Keywords:adenosine antagonism    lysozyme release    polymorphonuclear leucocytes    superoxide release    xanthine derivatives.
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