Effect of xanthine derivatives on chemotactic polypeptide-induced superoxide and enzyme release from human polymorphonuclear leucocytes.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirano
T
T
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Ando
M
M
Suzuki
K
K
Furui
H
H
Miyamoto
K
K
Takagi
K
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D008297:Male; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C058491:1-methyl-3-propylxanthine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D009113:Muramidase; D000243:Adenosine Deaminase; D000241:Adenosine; C046489:1,3-dipropylxanthine