Propentofylline inhibits polymorphonuclear leukocyte recruitment in vivo by a mechanism involving adenosine A2A receptors.
Propentofylline is an atypical xanthine derivative that blocks adenosine uptake and has been shown to protect against ischemia-induced cerebral damage. We have studied the effect of propentofylline on recruitment of polymorphonuclear leukocytes during acute peritonitis induced by zymosan in mice. Following i.p. injection of zymosan, recruitment of polymorphonuclear leukocytes, reflected by myeloperoxidase activity in the peritoneal cavity, increased from 2 h onwards, peaked at 4 h and then decreased gradually. Propentofylline antagonized the zymosan-induced peritoneal myeloperoxidase accumulation in a concentration-dependent manner. This effect of propentofylline was counteracted by the non-selective adenosine receptor antagonist theophylline (50 mg/kg), and by the selective adenosine A2A receptor antagonists, 4-amino-8-chloro-1-phenyl-[1,2,4]-triazolo[4,3-a]quinoxaline (CP 66713) and 1,3-dipropyl-8-[3,4-dimethoxystyryl]-7-methylxanthine (KF 17387) (both at 2 mg/kg). The results indicate that propentofylline can reduce polymorphonuclear leukocyte recruitment in vivo and that this effect is related to an action on adenosine A2A receptors.
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
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Zhang
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Raud
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Hedqvist
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BB
Fredholm
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects*; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D058915:Purinergic P1 Receptor Antagonists; D011719:Pyrazines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology*; D015054:Zymosan / Q000493:pharmacokinetics / Q000494:pharmacology
D000897:Anti-Ulcer Agents; C104314:KF 17387; D058915:Purinergic P1 Receptor Antagonists; D011719:Pyrazines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014970:Xanthines; C032114:propentofylline; D015054:Zymosan; C072107:CP 66713